This application is a continuation of U.S. application Ser. No. 14/887,605, filed Oct. 20, 2015, which is a continuation of U.S. application Ser. No. 13/190,391, filed Jul. 25, 2011, which claims the benefit of priority to U.S. Provisional Application Nos. 61/368,217, filed Jul. 27, 2010; 61/414,310, filed Nov. 16, 2010; and 61/485,536, filed May 12, 2011, all of which are hereby incorporated by reference.
TECHNICAL FIELD The present disclosure relates to molecular diagnostic assays that provide information concerning methods to use gene expression profiles to determine prognostic information for cancer patients. Specifically, the present disclosure provides genes and microRNAs, the expression levels of which may be used to determine the likelihood that a prostate cancer patient will experience a local or distant cancer recurrence.
INTRODUCTION Prostate cancer is the most common solid malignancy in men and the second most common cause of cancer-related death in men in North America and the European Union (EU). In 2008, over 180,000 patients will be diagnosed with prostate cancer in the United States alone and nearly 30,000 will die of this disease. Age is the single most important risk factor for the development of prostate cancer, and applies across all racial groups that have been studied. With the aging of the U.S. population, it is projected that the annual incidence of prostate cancer will double by 2025 to nearly 400,000 cases per year.
Since the introduction of prostate-specific antigen (PSA) screening in the 1990's, the proportion of patients presenting with clinically evident disease has fallen dramatically such that patients categorized as “low risk” now constitute half of new diagnoses today. PSA is used as a tumor marker to determine the presence of prostate cancer as high PSA levels are associated with prostate cancer. Despite a growing proportion of localized prostate cancer patients presenting with low-risk features such as low stage (T1) disease, greater than 90% of patients in the US still undergo definitive therapy, including prostatectomy or radiation. Only about 15% of these patients would develop metastatic disease and die from their prostate cancer, even in the absence of definitive therapy. A. Bill-Axelson, et al., J Nat'l Cancer Inst. 100(16):1144-1154 (2008). Therefore, the majority of prostate cancer patients are being over-treated.
Estimates of recurrence risk and treatment decisions in prostate cancer are currently based primarily on PSA levels and/or tumor stage. Although tumor stage has been demonstrated to have significant association with outcome sufficient to be included in pathology reports, the College of American Pathologists Consensus Statement noted that variations in approach to the acquisition, interpretation, reporting, and analysis of this information exist. C. Compton, et al., Arch Pathol Lab Med 124:979-992 (2000). As a consequence, existing pathologic staging methods have been criticized as lacking reproducibility and therefore may provide imprecise estimates of individual patient risk.
SUMMARY This application discloses molecular assays that involve measurement of expression level(s) of one or more genes, gene subsets, microRNAs, or one or more microRNAs in combination with one or more genes or gene subsets, from a biological sample obtained from a prostate cancer patient, and analysis of the measured expression levels to provide information concerning the likelihood of cancer recurrence. For example, the likelihood of cancer recurrence could be described in terms of a score based on clinical or biochemical recurrence-free interval.
In addition, this application discloses molecular assays that involve measurement of expression level(s) of one or more genes, gene subsets, microRNAs, or one or more microRNAs in combination with one or more genes or gene subsets, from a biological sample obtained to identify a risk classification for a prostate cancer patient. For example, patients may be stratified using expression level(s) of one or more genes or microRNAs associated, positively or negatively, with cancer recurrence or death from cancer, or with a prognostic factor. In an exemplary embodiment, the prognostic factor is Gleason pattern.
The biological sample may be obtained from standard methods, including surgery, biopsy, or bodily fluids. It may comprise tumor tissue or cancer cells, and, in some cases, histologically normal tissue, e.g., histologically normal tissue adjacent the tumor tissue. In exemplary embodiments, the biological sample is positive or negative for a TMPRSS2 fusion.
In exemplary embodiments, expression level(s) of one or more genes and/or microRNAs that are associated, positively or negatively, with a particular clinical outcome in prostate cancer are used to determine prognosis and appropriate therapy. The genes disclosed herein may be used alone or arranged in functional gene subsets, such as cell adhesion/migration, immediate-early stress response, and extracellular matrix-associated. Each gene subset comprises the genes disclosed herein, as well as genes that are co-expressed with one or more of the disclosed genes. The calculation may be performed on a computer, programmed to execute the gene expression analysis. The microRNAs disclosed herein may also be used alone or in combination with any one or more of the microRNAs and/or genes disclosed.
In exemplary embodiments, the molecular assay may involve expression levels for at least two genes. The genes, or gene subsets, may be weighted according to strength of association with prognosis or tumor microenvironment. In another exemplary embodiment, the molecular assay may involve expression levels of at least one gene and at least one microRNA. The gene-microRNA combination may be selected based on the likelihood that the gene-microRNA combination functionally interact.
BRIEF DESCRIPTION OF THE DRAWING FIG. 1 shows the distribution of clinical and pathology assessments of biopsy Gleason score, baseline PSA level, and clinical T-stage.
DEFINITIONS Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Singleton et al., Dictionary of Microbiology and Molecular Biology 2nd ed., J. Wiley & Sons (New York, N.Y. 1994), and March, Advanced Organic Chemistry Reactions, Mechanisms and Structure 4th ed., John Wiley & Sons (New York, N.Y. 1992), provide one skilled in the art with a general guide to many of the terms used in the present application.
One skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which could be used in the practice of the present invention. Indeed, the present invention is in no way limited to the methods and materials described herein. For purposes of the invention, the following terms are defined below.
The terms “tumor” and “lesion” as used herein, refer to all neoplastic cell growth and proliferation, whether malignant or benign, and all pre-cancerous and cancerous cells and tissues. Those skilled in the art will realize that a tumor tissue sample may comprise multiple biological elements, such as one or more cancer cells, partial or fragmented cells, tumors in various stages, surrounding histologically normal-appearing tissue, and/or macro or micro-dissected tissue.
The terms “cancer” and “cancerous” refer to or describe the physiological condition in mammals that is typically characterized by unregulated cell growth. Examples of cancer in the present disclosure include cancer of the urogenital tract, such as prostate cancer.
The “pathology” of cancer includes all phenomena that compromise the well-being of the patient. This includes, without limitation, abnormal or uncontrollable cell growth, metastasis, interference with the normal functioning of neighboring cells, release of cytokines or other secretory products at abnormal levels, suppression or aggravation of inflammatory or immunological response, neoplasia, premalignancy, malignancy, invasion of surrounding or distant tissues or organs, such as lymph nodes, etc.
As used herein, the term “prostate cancer” is used interchangeably and in the broadest sense refers to all stages and all forms of cancer arising from the tissue of the prostate gland.
According to the tumor, node, metastasis (TNM) staging system of the American Joint Committee on Cancer (AJCC), AJCC Cancer Staging Manual (7th Ed., 2010), the various stages of prostate cancer are defined as follows: Tumor: T1: clinically inapparent tumor not palpable or visible by imaging, T1a: tumor incidental histological finding in 5% or less of tissue resected, T1b: tumor incidental histological finding in more than 5% of tissue resected, T1c: tumor identified by needle biopsy; T2: tumor confined within prostate, T2a: tumor involves one half of one lobe or less, T2b: tumor involves more than half of one lobe, but not both lobes, T2c: tumor involves both lobes; T3: tumor extends through the prostatic capsule, T3a: extracapsular extension (unilateral or bilateral), T3b: tumor invades seminal vesicle(s); T4: tumor is fixed or invades adjacent structures other than seminal vesicles (bladder neck, external sphincter, rectum, levator muscles, or pelvic wall). Node: N0: no regional lymph node metastasis; N1: metastasis in regional lymph nodes. Metastasis: M0: no distant metastasis; M1: distant metastasis present.
The Gleason Grading system is used to help evaluate the prognosis of men with prostate cancer. Together with other parameters, it is incorporated into a strategy of prostate cancer staging, which predicts prognosis and helps guide therapy. A Gleason “score” or “grade” is given to prostate cancer based upon its microscopic appearance. Tumors with a low Gleason score typically grow slowly enough that they may not pose a significant threat to the patients in their lifetimes. These patients are monitored (“watchful waiting” or “active surveillance”) over time. Cancers with a higher Gleason score are more aggressive and have a worse prognosis, and these patients are generally treated with surgery (e.g., radical prostectomy) and, in some cases, therapy (e.g., radiation, hormone, ultrasound, chemotherapy). Gleason scores (or sums) comprise grades of the two most common tumor patterns. These patterns are referred to as Gleason patterns 1-5, with pattern 1 being the most well-differentiated. Most have a mixture of patterns. To obtain a Gleason score or grade, the dominant pattern is added to the second most prevalent pattern to obtain a number between 2 and 10. The Gleason Grades include: G1: well differentiated (slight anaplasia) (Gleason 2-4); G2: moderately differentiated (moderate anaplasia) (Gleason 5-6); G3-4: poorly differentiated/undifferentiated (marked anaplasia) (Gleason 7-10).
Stage groupings: Stage I: T1a N0M0 G1; Stage II: (T1a N0 M0 G2-4) or (T1b, c, T1, T2, N0 M0 Any G); Stage III: T3 N0 M0 Any G; Stage IV: (T4 N0 M0 Any G) or (Any T N1 M0 Any G) or (Any T Any N M1 Any G).
As used herein, the term “tumor tissue” refers to a biological sample containing one or more cancer cells, or a fraction of one or more cancer cells. Those skilled in the art will recognize that such biological sample may additionally comprise other biological components, such as histologically appearing normal cells (e.g., adjacent the tumor), depending upon the method used to obtain the tumor tissue, such as surgical resection, biopsy, or bodily fluids.
As used herein, the term “AUA risk group” refers to the 2007 updated American Urological Association (AUA) guidelines for management of clinically localized prostate cancer, which clinicians use to determine whether a patient is at low, intermediate, or high risk of biochemical (PSA) relapse after local therapy.
As used herein, the term “adjacent tissue (AT)” refers to histologically “normal” cells that are adjacent a tumor. For example, the AT expression profile may be associated with disease recurrence and survival.
As used herein “non-tumor prostate tissue” refers to histologically normal-appearing tissue adjacent a prostate tumor.
Prognostic factors are those variables related to the natural history of cancer, which influence the recurrence rates and outcome of patients once they have developed cancer. Clinical parameters that have been associated with a worse prognosis include, for example, increased tumor stage, PSA level at presentation, and Gleason grade or pattern. Prognostic factors are frequently used to categorize patients into subgroups with different baseline relapse risks.
The term “prognosis” is used herein to refer to the likelihood that a cancer patient will have a cancer-attributable death or progression, including recurrence, metastatic spread, and drug resistance, of a neoplastic disease, such as prostate cancer. For example, a “good prognosis” would include long term survival without recurrence and a “bad prognosis” would include cancer recurrence.
As used herein, the term “expression level” as applied to a gene refers to the normalized level of a gene product, e.g. the normalized value determined for the RNA expression level of a gene or for the polypeptide expression level of a gene.
The term “gene product” or “expression product” are used herein to refer to the RNA (ribonucleic acid) transcription products (transcripts) of the gene, including mRNA, and the polypeptide translation products of such RNA transcripts. A gene product can be, for example, an unspliced RNA, an mRNA, a splice variant mRNA, a microRNA, a fragmented RNA, a polypeptide, a post-translationally modified polypeptide, a splice variant polypeptide, etc.
The term “RNA transcript” as used herein refers to the RNA transcription products of a gene, including, for example, mRNA, an unspliced RNA, a splice variant mRNA, a microRNA, and a fragmented RNA.
The term “microRNA” is used herein to refer to a small, non-coding, single-stranded RNA of ˜18-25 nucleotides that may regulate gene expression. For example, when associated with the RNA-induced silencing complex (RISC), the complex binds to specific mRNA targets and causes translation repression or cleavage of these mRNA sequences.
Unless indicated otherwise, each gene name used herein corresponds to the Official Symbol assigned to the gene and provided by Entrez Gene (URL: www.ncbi.nlm.nih.gov/sites/entrez) as of the filing date of this application.
The terms “correlated” and “associated” are used interchangeably herein to refer to the association between two measurements (or measured entities). The disclosure provides genes, gene subsets, microRNAs, or microRNAs in combination with genes or gene subsets, the expression levels of which are associated with tumor stage. For example, the increased expression level of a gene or microRNA may be positively correlated (positively associated) with a good or positive prognosis. Such a positive correlation may be demonstrated statistically in various ways, e.g. by a cancer recurrence hazard ratio less than one. In another example, the increased expression level of a gene or microRNA may be negatively correlated (negatively associated) with a good or positive prognosis. In that case, for example, the patient may experience a cancer recurrence.
The terms “good prognosis” or “positive prognosis” as used herein refer to a beneficial clinical outcome, such as long-term survival without recurrence. The terms “bad prognosis” or “negative prognosis” as used herein refer to a negative clinical outcome, such as cancer recurrence.
The term “risk classification” means a grouping of subjects by the level of risk (or likelihood) that the subject will experience a particular clinical outcome. A subject may be classified into a risk group or classified at a level of risk based on the methods of the present disclosure, e.g. high, medium, or low risk. A “risk group” is a group of subjects or individuals with a similar level of risk for a particular clinical outcome.
The term “long-term” survival is used herein to refer to survival for a particular time period, e.g., for at least 5 years, or for at least 10 years.
The term “recurrence” is used herein to refer to local or distant recurrence (i.e., metastasis) of cancer. For example, prostate cancer can recur locally in the tissue next to the prostate or in the seminal vesicles. The cancer may also affect the surrounding lymph nodes in the pelvis or lymph nodes outside this area. Prostate cancer can also spread to tissues next to the prostate, such as pelvic muscles, bones, or other organs. Recurrence can be determined by clinical recurrence detected by, for example, imaging study or biopsy, or biochemical recurrence detected by, for example, sustained follow-up prostate-specific antigen (PSA) levels ≥0.4 ng/mL or the initiation of salvage therapy as a result of a rising PSA level.
The term “clinical recurrence-free interval (cRFI)” is used herein as time (in months) from surgery to first clinical recurrence or death due to clinical recurrence of prostate cancer. Losses due to incomplete follow-up, other primary cancers or death prior to clinical recurrence are considered censoring events; when these occur, the only information known is that up through the censoring time, clinical recurrence has not occurred in this subject. Biochemical recurrences are ignored for the purposes of calculating cRFI.
The term “biochemical recurrence-free interval (bRFI)” is used herein to mean the time (in months) from surgery to first biochemical recurrence of prostate cancer. Clinical recurrences, losses due to incomplete follow-up, other primary cancers, or death prior to biochemical recurrence are considered censoring events.
The term “Overall Survival (OS)” is used herein to refer to the time (in months) from surgery to death from any cause. Losses due to incomplete follow-up are considered censoring events. Biochemical recurrence and clinical recurrence are ignored for the purposes of calculating OS.
The term “Prostate Cancer-Specific Survival (PCSS)” is used herein to describe the time (in years) from surgery to death from prostate cancer. Losses due to incomplete follow-up or deaths from other causes are considered censoring events. Clinical recurrence and biochemical recurrence are ignored for the purposes of calculating PCSS.
The term “upgrading” or “upstaging” as used herein refers to a change in Gleason grade from 3+3 at the time of biopsy to 3+4 or greater at the time of radical prostatectomy (RP), or Gleason grade 3+4 at the time of biopsy to 4+3 or greater at the time of RP, or seminal vessical involvement (SVI), or extracapsular involvement (ECE) at the time of RP.
In practice, the calculation of the measures listed above may vary from study to study depending on the definition of events to be considered censored.
The term “microarray” refers to an ordered arrangement of hybridizable array elements, e.g. oligonucleotide or polynucleotide probes, on a substrate.
The term “polynucleotide” generally refers to any polyribonucleotide or polydeoxribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA. Thus, for instance, polynucleotides as defined herein include, without limitation, single- and double-stranded DNA, DNA including single- and double-stranded regions, single- and double-stranded RNA, and RNA including single- and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or include single- and double-stranded regions. In addition, the term “polynucleotide” as used herein refers to triple-stranded regions comprising RNA or DNA or both RNA and DNA. The strands in such regions may be from the same molecule or from different molecules. The regions may include all of one or more of the molecules, but more typically involve only a region of some of the molecules. One of the molecules of a triple-helical region often is an oligonucleotide. The term “polynucleotide” specifically includes cDNAs. The term includes DNAs (including cDNAs) and RNAs that contain one or more modified bases. Thus, DNAs or RNAs with backbones modified for stability or for other reasons, are “polynucleotides” as that term is intended herein. Moreover, DNAs or RNAs comprising unusual bases, such as inosine, or modified bases, such as tritiated bases, are included within the term “polynucleotides” as defined herein. In general, the term “polynucleotide” embraces all chemically, enzymatically and/or metabolically modified forms of unmodified polynucleotides, as well as the chemical forms of DNA and RNA characteristic of viruses and cells, including simple and complex cells.
The term “oligonucleotide” refers to a relatively short polynucleotide, including, without limitation, single-stranded deoxyribonucleotides, single- or double-stranded ribonucleotides, RNArDNA hybrids and double-stranded DNAs. Oligonucleotides, such as single-stranded DNA probe oligonucleotides, are often synthesized by chemical methods, for example using automated oligonucleotide synthesizers that are commercially available. However, oligonucleotides can be made by a variety of other methods, including in vitro recombinant DNA-mediated techniques and by expression of DNAs in cells and organisms.
The term “Ct” as used herein refers to threshold cycle, the cycle number in quantitative polymerase chain reaction (qPCR) at which the fluorescence generated within a reaction well exceeds the defined threshold, i.e. the point during the reaction at which a sufficient number of amplicons have accumulated to meet the defined threshold.
The term “Cp” as used herein refers to “crossing point.” The Cp value is calculated by determining the second derivatives of entire qPCR amplification curves and their maximum value. The Cp value represents the cycle at which the increase of fluorescence is highest and where the logarithmic phase of a PCR begins.
The terms “threshold” or “thresholding” refer to a procedure used to account for non-linear relationships between gene expression measurements and clinical response as well as to further reduce variation in reported patient scores. When thresholding is applied, all measurements below or above a threshold are set to that threshold value. Non-linear relationship between gene expression and outcome could be examined using smoothers or cubic splines to model gene expression in Cox PH regression on recurrence free interval or logistic regression on recurrence status. D. Cox, Journal of the Royal Statistical Society, Series B 34:187-220 (1972). Variation in reported patient scores could be examined as a function of variability in gene expression at the limit of quantitation and/or detection for a particular gene.
As used herein, the term “amplicon,” refers to pieces of DNA that have been synthesized using amplification techniques, such as polymerase chain reactions (PCR) and ligase chain reactions.
“Stringency” of hybridization reactions is readily determinable by one of ordinary skill in the art, and generally is an empirical calculation dependent upon probe length, washing temperature, and salt concentration. In general, longer probes require higher temperatures for proper annealing, while shorter probes need lower temperatures. Hybridization generally depends on the ability of denatured DNA to re-anneal when complementary strands are present in an environment below their melting temperature. The higher the degree of desired homology between the probe and hybridizable sequence, the higher the relative temperature which can be used. As a result, it follows that higher relative temperatures would tend to make the reaction conditions more stringent, while lower temperatures less so. For additional details and explanation of stringency of hybridization reactions, see Ausubel et al., Current Protocols in Molecular Biology (Wiley Interscience Publishers, 1995).
“Stringent conditions” or “high stringency conditions”, as defined herein, typically: (1) employ low ionic strength and high temperature for washing, for example 0.015 M sodium chloride/0.0015 M sodium citrate/0.1% sodium dodecyl sulfate at 50° C.; (2) employ during hybridization a denaturing agent, such as formamide, for example, 50% (v/v) formamide with 0.1% bovine serum albumin/0.1% Ficoll/0.1% polyvinylpyrrolidone/50 mM sodium phosphate buffer at pH 6.5 with 750 mM sodium chloride, 75 mM sodium citrate at 42° C.; or (3) employ 50% formamide, 5×SSC (0.75 M NaCl, 0.075 M sodium citrate), 50 mM sodium phosphate (pH 6.8), 0.1% sodium pyrophosphate, 5×Denhardt's solution, sonicated salmon sperm DNA (50 μg/ml), 0.1% SDS, and 10% dextran sulfate at 42° C., with washes at 42° C. in 0.2×SSC (sodium chloride/sodium citrate) and 50% formamide, followed by a high-stringency wash consisting of 0.1×SSC containing EDTA at 55° C.
“Moderately stringent conditions” may be identified as described by Sambrook et al., Molecular Cloning: A Laboratory Manual, New York: Cold Spring Harbor Press, 1989, and include the use of washing solution and hybridization conditions (e.g., temperature, ionic strength and % SDS) less stringent that those described above. An example of moderately stringent conditions is overnight incubation at 37° C. in a solution comprising: 20% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5×Denhardt's solution, 10% dextran sulfate, and 20 mg/ml denatured sheared salmon sperm DNA, followed by washing the filters in 1×SSC at about 37-500 C. The skilled artisan will recognize how to adjust the temperature, ionic strength, etc. as necessary to accommodate factors such as probe length and the like.
The terms “splicing” and “RNA splicing” are used interchangeably and refer to RNA processing that removes introns and joins exons to produce mature mRNA with continuous coding sequence that moves into the cytoplasm of an eukaryotic cell.
The terms “co-express” and “co-expressed”, as used herein, refer to a statistical correlation between the amounts of different transcript sequences across a population of different patients. Pairwise co-expression may be calculated by various methods known in the art, e.g., by calculating Pearson correlation coefficients or Spearman correlation coefficients. Co-expressed gene cliques may also be identified using graph theory. An analysis of co-expression may be calculated using normalized expression data. A gene is said to be co-expressed with a particular disclosed gene when the expression level of the gene exhibits a Pearson correlation coefficient greater than or equal to 0.6.
A “computer-based system” refers to a system of hardware, software, and data storage medium used to analyze information. The minimum hardware of a patient computer-based system comprises a central processing unit (CPU), and hardware for data input, data output (e.g., display), and data storage. An ordinarily skilled artisan can readily appreciate that any currently available computer-based systems and/or components thereof are suitable for use in connection with the methods of the present disclosure. The data storage medium may comprise any manufacture comprising a recording of the present information as described above, or a memory access device that can access such a manufacture.
To “record” data, programming or other information on a computer readable medium refers to a process for storing information, using any such methods as known in the art. Any convenient data storage structure may be chosen, based on the means used to access the stored information. A variety of data processor programs and formats can be used for storage, e.g. word processing text file, database format, etc.
A “processor” or “computing means” references any hardware and/or software combination that will perform the functions required of it. For example, a suitable processor may be a programmable digital microprocessor such as available in the form of an electronic controller, mainframe, server or personal computer (desktop or portable). Where the processor is programmable, suitable programming can be communicated from a remote location to the processor, or previously saved in a computer program product (such as a portable or fixed computer readable storage medium, whether magnetic, optical or solid state device based). For example, a magnetic medium or optical disk may carry the programming, and can be read by a suitable reader communicating with each processor at its corresponding station.
As used herein, the terms “active surveillance” and “watchful waiting” mean closely monitoring a patient's condition without giving any treatment until symptoms appear or change. For example, in prostate cancer, watchful waiting is usually used in older men with other medical problems and early-stage disease.
As used herein, the term “surgery” applies to surgical methods undertaken for removal of cancerous tissue, including pelvic lymphadenectomy, radical prostatectomy, transurethral resection of the prostate (TURP), excision, dissection, and tumor biopsy/removal. The tumor tissue or sections used for gene expression analysis may have been obtained from any of these methods.
As used herein, the term “therapy” includes radiation, hormonal therapy, cryosurgery, chemotherapy, biologic therapy, and high-intensity focused ultrasound.
As used herein, the term “TMPRSS fusion” and “TMPRSS2 fusion” are used interchangeably and refer to a fusion of the androgen-driven TMPRSS2 gene with the ERG oncogene, which has been demonstrated to have a significant association with prostate cancer. S. Perner, et al., Urologe A. 46(7):754-760 (2007); S. A. Narod, et al., Br J Cancer 99(6):847-851 (2008). As used herein, positive TMPRSS fusion status indicates that the TMPRSS fusion is present in a tissue sample, whereas negative TMPRSS fusion status indicates that the TMPRSS fusion is not present in a tissue sample. Experts skilled in the art will recognize that there are numerous ways to determine TMPRSS fusion status, such as real-time, quantitative PCR or high-throughput sequencing. See, e.g., K. Mertz, et al., Neoplasis 9(3):200-206 (2007); C. Maher, Nature 458(7234):97-101 (2009).
Gene Expression Methods Using Genes, Gene Subsets, and Micrornas The present disclosure provides molecular assays that involve measurement of expression level(s) of one or more genes, gene subsets, microRNAs, or one or more microRNAs in combination with one or more genes or gene subsets, from a biological sample obtained from a prostate cancer patient, and analysis of the measured expression levels to provide information concerning the likelihood of cancer recurrence.
The present disclosure further provides methods to classify a prostate tumor based on expression level(s) of one or more genes and/or microRNAs. The disclosure further provides genes and/or microRNAs that are associated, positively or negatively, with a particular prognostic outcome. In exemplary embodiments, the clinical outcomes include cRFI and bRFI. In another embodiment, patients may be classified in risk groups based on the expression level(s) of one or more genes and/or microRNAs that are associated, positively or negatively, with a prognostic factor. In an exemplary embodiment, that prognostic factor is Gleason pattern.
Various technological approaches for determination of expression levels of the disclosed genes and microRNAs are set forth in this specification, including, without limitation, RT-PCR, microarrays, high-throughput sequencing, serial analysis of gene expression (SAGE) and Digital Gene Expression (DGE), which will be discussed in detail below. In particular aspects, the expression level of each gene or microRNA may be determined in relation to various features of the expression products of the gene including exons, introns, protein epitopes and protein activity.
The expression level(s) of one or more genes and/or microRNAs may be measured in tumor tissue. For example, the tumor tissue may obtained upon surgical removal or resection of the tumor, or by tumor biopsy. The tumor tissue may be or include histologically “normal” tissue, for example histologically “normal” tissue adjacent to a tumor. The expression level of genes and/or microRNAs may also be measured in tumor cells recovered from sites distant from the tumor, for example circulating tumor cells, body fluid (e.g., urine, blood, blood fraction, etc.).
The expression product that is assayed can be, for example, RNA or a polypeptide. The expression product may be fragmented. For example, the assay may use primers that are complementary to target sequences of an expression product and could thus measure full transcripts as well as those fragmented expression products containing the target sequence. Further information is provided in Table A (inserted in specification prior to claims).
The RNA expression product may be assayed directly or by detection of a cDNA product resulting from a PCR-based amplification method, e.g., quantitative reverse transcription polymerase chain reaction (qRT-PCR). (See e.g., U.S. Pat. No. 7,587,279). Polypeptide expression product may be assayed using immunohistochemistry (IHC). Further, both RNA and polypeptide expression products may also be is assayed using microarrays.
Clinical Utility Prostate cancer is currently diagnosed using a digital rectal exam (DRE) and Prostate-specific antigen (PSA) test. If PSA results are high, patients will generally undergo a prostate tissue biopsy. The pathologist will review the biopsy samples to check for cancer cells and determine a Gleason score. Based on the Gleason score, PSA, clinical stage, and other factors, the physician must make a decision whether to monitor the patient, or treat the patient with surgery and therapy.
At present, clinical decision-making in early stage prostate cancer is governed by certain histopathologic and clinical factors. These include: (1) tumor factors, such as clinical stage (e.g. T1, T2), PSA level at presentation, and Gleason grade, that are very strong prognostic factors in determining outcome; and (2) host factors, such as age at diagnosis and co-morbidity. Because of these factors, the most clinically useful means of stratifying patients with localized disease according to prognosis has been through multifactorial staging, using the clinical stage, the serum PSA level, and tumor grade (Gleason grade) together. In the 2007 updated American Urological Association (AUA) guidelines for management of clinically localized prostate cancer, these parameters have been grouped to determine whether a patient is at low, intermediate, or high risk of biochemical (PSA) relapse after local therapy. I. Thompson, et al., Guideline for the management of clinically localized prostate cancer, J Urol. 177(6):2106-31 (2007).
Although such classifications have proven to be helpful in distinguishing patients with localized disease who may need adjuvant therapy after surgery/radiation, they have less ability to discriminate between indolent cancers, which do not need to be treated with local therapy, and aggressive tumors, which require local therapy. In fact, these algorithms are of increasingly limited use for deciding between conservative management and definitive therapy because the bulk of prostate cancers diagnosed in the PSA screening era now present with clinical stage T1c and PSA ≤10 ng/mL.
Patients with T1 prostate cancer have disease that is not clinically apparent but is discovered either at transurethral resection of the prostate (TURP, T1a, T1b) or at biopsy performed because of an elevated PSA (>4 ng/mL, T1c). Approximately 80% of the cases presenting in 2007 are clinical T1 at diagnosis. In a Scandinavian trial, OS at 10 years was 85% for patients with early stage prostate cancer (T1/T2) and Gleason score <7, after radical prostatectomy.
Patients with T2 prostate cancer have disease that is clinically evident and is organ confined; patients with T3 tumors have disease that has penetrated the prostatic capsule and/or has invaded the seminal vesicles. It is known from surgical series that clinical staging underestimates pathological stage, so that about 20% of patients who are clinically T2 will be pT3 after prostatectomy. Most of patients with T2 or T3 prostate cancer are treated with local therapy, either prostatectomy or radiation. The data from the Scandinavian trial suggest that for T2 patients with Gleason grade ≤7, the effect of prostatectomy on survival is at most 5% at 10 years; the majority of patients do not benefit from surgical treatment at the time of diagnosis. For T2 patients with Gleason >7 or for T3 patients, the treatment effect of prostatectomy is assumed to be significant but has not been determined in randomized trials. It is known that these patients have a significant risk (10-30%) of recurrence at 10 years after local treatment, however, there are no prospective randomized trials that define the optimal local treatment (radical prostatectomy, radiation) at diagnosis, which patients are likely to benefit from neo-adjuvant/adjuvant androgen deprivation therapy, and whether treatment (androgen deprivation, chemotherapy) at the time of biochemical failure (elevated PSA) has any clinical benefit.
Accurately determining Gleason scores from needle biopsies presents several technical challenges. First, interpreting histology that is “borderline” between Gleason pattern is highly subjective, even for urologic pathologists. Second, incomplete biopsy sampling is yet another reason why the “predicted” Gleason score on biopsy does not always correlate with the actual “observed” Gleason score of the prostate cancer in the gland itself. Hence, the accuracy of Gleason scoring is dependent upon not only the expertise of the pathologist reading the slides, but also on the completeness and adequacy of the prostate biopsy sampling strategy. T. Stamey, Urology 45:2-12 (1995). The gene/microRNA expression assay and associated information provided by the practice of the methods disclosed herein provide a molecular assay method to facilitate optimal treatment decision-making in early stage prostate cancer. An exemplary embodiment provides genes and microRNAs, the expression levels of which are associated (positively or negatively) with prostate cancer recurrence. For example, such a clinical tool would enable physicians to identify T2/T3 patients who are likely to recur following definitive therapy and need adjuvant treatment.
In addition, the methods disclosed herein may allow physicians to classify tumors, at a molecular level, based on expression level(s) of one or more genes and/or microRNAs that are significantly associated with prognostic factors, such as Gleason pattern and TMPRSS fusion status. These methods would not be impacted by the technical difficulties of intra-patient variability, histologically determining Gleason pattern in biopsy samples, or inclusion of histologically normal appearing tissue adjacent to tumor tissue. Multi-analyte gene/microRNA expression tests can be used to measure the expression level of one or more genes and/or microRNAs involved in each of several relevant physiologic processes or component cellular characteristics. The methods disclosed herein may group the genes and/or microRNAs. The grouping of genes and microRNAs may be performed at least in part based on knowledge of the contribution of those genes and/or microRNAs according to physiologic functions or component cellular characteristics, such as in the groups discussed above. Furthermore, one or more microRNAs may be combined with one or moregenes. The gene-microRNA combination may be selected based on the likelihood that the gene-microRNA combination functionally interact. The formation of groups (or gene subsets), in addition, can facilitate the mathematical weighting of the contribution of various expression levels to cancer recurrence. The weighting of a gene/microRNA group representing a physiological process or component cellular characteristic can reflect the contribution of that process or characteristic to the pathology of the cancer and clinical outcome.
Optionally, the methods disclosed may be used to classify patients by risk, for example risk of recurrence. Patients can be partitioned into subgroups (e.g., tertiles or quartiles) and the values chosen will define subgroups of patients with respectively greater or lesser risk.
The utility of a disclosed gene marker in predicting prognosis may not be unique to that marker. An alternative marker having an expression pattern that is parallel to that of a disclosed gene may be substituted for, or used in addition to, that co-expressed gene or microRNA. Due to the co-expression of such genes or microRNAs, substitution of expression level values should have little impact on the overall utility of the test. The closely similar expression patterns of two genes or microRNAs may result from involvement of both genes or microRNAs in the same process and/or being under common regulatory control in prostate tumor cells. The present disclosure thus contemplates the use of such co-expressed genes,gene subsets, or microRNAs as substitutes for, or in addition to, genes of the present disclosure.
Methods of Assaying Expression Levels of a Gene Product The methods and compositions of the present disclosure will employ, unless otherwise indicated, conventional techniques of molecular biology (including recombinant techniques), microbiology, cell biology, and biochemistry, which are within the skill of the art. Exemplary techniques are explained fully in the literature, such as, “Molecular Cloning: A Laboratory Manual”, 2nd edition (Sambrook et al., 1989); “Oligonucleotide Synthesis” (M. J. Gait, ed., 1984); “Animal Cell Culture” (R. I. Freshney, ed., 1987); “Methods in Enzymology” (Academic Press, Inc.); “Handbook of Experimental Immunology”, 4th edition (D. M. Weir & C. C. Blackwell, eds., Blackwell Science Inc., 1987); “Gene Transfer Vectors for Mammalian Cells” (J. M. Miller & M. P. Calos, eds., 1987); “Current Protocols in Molecular Biology” (F. M. Ausubel et al., eds., 1987); and “PCR: The Polymerase Chain Reaction”, (Mullis et al., eds., 1994).
Methods of gene expression profiling include methods based on hybridization analysis of polynucleotides, methods based on sequencing of polynucleotides, and proteomics-based methods. Exemplary methods known in the art for the quantification of RNA expression in a sample include northern blotting and in situ hybridization (Parker & Barnes, Methods in Molecular Biology 106:247-283 (1999)); RNAse protection assays (Hod, Biotechniques 13:852-854 (1992)); and PCR-based methods, such as reverse transcription PCT (RT-PCR) (Weis et al., Trends in Genetics 8:263-264 (1992)). Antibodies may be employed that can recognize sequence-specific duplexes, including DNA duplexes, RNA duplexes, and DNA-RNA hybrid duplexes or DNA-protein duplexes. Representative methods for sequencing-based gene expression analysis include Serial Analysis of Gene Expression (SAGE), and gene expression analysis by massively parallel signature sequencing (MPSS).
Reverse Transcriptase PCR (RT-PCR)
Typically, mRNA or microRNA is isolated from a test sample. The starting material is typically total RNA isolated from a human tumor, usually from a primary tumor. Optionally, normal tissues from the same patient can be used as an internal control. Such normal tissue can be histologically-appearing normal tissue adjacent a tumor. mRNA or microRNA can be extracted from a tissue sample, e.g., from a sample that is fresh, frozen (e.g. fresh frozen), or paraffin-embedded and fixed (e.g. formalin-fixed).
General methods for mRNA and microRNA extraction are well known in the art and are disclosed in standard textbooks of molecular biology, including Ausubel et al., Current Protocols of Molecular Biology, John Wiley and Sons (1997). Methods for RNA extraction from paraffin embedded tissues are disclosed, for example, in Rupp and Locker, Lab Invest. 56:A67 (1987), and De Andres et al., BioTechniques 18:42044 (1995). In particular, RNA isolation can be performed using a purification kit, buffer set and protease from commercial manufacturers, such as Qiagen, according to the manufacturer's instructions. For example, total RNA from cells in culture can be isolated using Qiagen RNeasy mini-columns. Other commercially available RNA isolation kits include MasterPureTM Complete DNA and RNA Purification Kit (EPICENTRE®, Madison, Wis.), and Paraffin Block RNA Isolation Kit (Ambion, Inc.). Total RNA from tissue samples can be isolated using RNA Stat-60 (Tel-Test). RNA prepared from tumor can be isolated, for example, by cesium chloride density gradient centrifugation.
The sample containing the RNA is then subjected to reverse transcription to produce cDNA from the RNA template, followed by exponential amplification in a PCR reaction. The two most commonly used reverse transcriptases are avilo myeloblastosis virus reverse transcriptase (AMV-RT) and Moloney murine leukemia virus reverse transcriptase (MMLV-RT). The reverse transcription step is typically primed using specific primers, random hexamers, or oligo-dT primers, depending on the circumstances and the goal of expression profiling. For example, extracted RNA can be reverse-transcribed using a GeneAmp RNA PCR kit (Perkin Elmer, CA, USA), following the manufacturer's instructions. The derived cDNA can then be used as a template in the subsequent PCR reaction.
PCR-based methods use a thermostable DNA-dependent DNA polymerase, such as a Taq DNA polymerase. For example, TaqMan® PCR typically utilizes the 5′-nuclease activity of Taq or Tth polymerase to hydrolyze a hybridization probe bound to its target amplicon, but any enzyme with equivalent 5′ nuclease activity can be used. Two oligonucleotide primers are used to generate an amplicon typical of a PCR reaction product. A third oligonucleotide, or probe, can be designed to facilitate detection of a nucleotide sequence of the amplicon located between the hybridization sites the two PCR primers. The probe can be detectably labeled, e.g., with a reporter dye, and can further be provided with both a fluorescent dye, and a quencher fluorescent dye, as in a Taqman® probe configuration. Where a Taqman® probe is used, during the amplification reaction, the Taq DNA polymerase enzyme cleaves the probe in a template-dependent manner. The resultant probe fragments disassociate in solution, and signal from the released reporter dye is free from the quenching effect of the second fluorophore. One molecule of reporter dye is liberated for each new molecule synthesized, and detection of the unquenched reporter dye provides the basis for quantitative interpretation of the data.
TaqMan® RT-PCR can be performed using commercially available equipment, such as, for example, high-throughput platforms such as the ABI PRISM 7700 Sequence Detection System® (Perkin-Elmer-Applied Biosystems, Foster City, Calif., USA), or Lightcycler (Roche Molecular Biochemicals, Mannheim, Germany). In a preferred embodiment, the procedure is run on a LightCycler® 480 (Roche Diagnostics) real-time PCR system, which is a microwell plate-based cycler platform.
5′-Nuclease assay data are commonly initially expressed as a threshold cycle (“CT”). Fluorescence values are recorded during every cycle and represent the amount of product amplified to that point in the amplification reaction. The threshold cycle (CT) is generally described as the point when the fluorescent signal is first recorded as statistically significant. Alternatively, data may be expressed as a crossing point (“Cp”). The Cp value is calculated by determining the second derivatives of entire qPCR amplification curves and their maximum value. The Cp value represents the cycle at which the increase of fluorescence is highest and where the logarithmic phase of a PCR begins.
To minimize errors and the effect of sample-to-sample variation, RT-PCR is usually performed using an internal standard. The ideal internal standard gene (also referred to as a reference gene) is expressed at a quite constant level among cancerous and non-cancerous tissue of the same origin (i.e., a level that is not significantly different among normal and cancerous tissues), and is not significantly affected by the experimental treatment (i.e., does not exhibit a significant difference in expression level in the relevant tissue as a result of exposure to chemotherapy), and expressed at a quite constant level among the same tissue taken from different patients. For example, reference genes useful in the methods disclosed herein should not exhibit significantly different expression levels in cancerous prostate as compared to normal prostate tissue. RNAs frequently used to normalize patterns of gene expression are mRNAs for the housekeeping genes glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) and β-actin. Exemplary reference genes used for normalization comprise one or more of the following genes: AAMP, ARF1, ATP5E, CLTC, GPS1, and PGK1. Gene expression measurements can be normalized relative to the mean of one or more (e.g., 2, 3, 4, 5, or more) reference genes. Reference-normalized expression measurements can range from 2 to 15, where a one unit increase generally reflects a 2-fold increase in RNA quantity.
Real time PCR is compatible both with quantitative competitive PCR, where internal competitor for each target sequence is used for normalization, and with quantitative comparative PCR using a normalization gene contained within the sample, or a housekeeping gene for RT-PCR. For further details see, e.g. Held et al., Genome Research 6:986-994 (1996).
The steps of a representative protocol for use in the methods of the present disclosure use fixed, paraffin-embedded tissues as the RNA source. For example, mRNA isolation, purification, primer extension and amplification can be performed according to methods available in the art. (see, e.g., Godfrey et al. J. Molec. Diagnostics 2: 84-91 (2000); Specht et al., Am. J. Pathol. 158: 419-29 (2001)). Briefly, a representative process starts with cutting about 10 μm thick sections of paraffin-embedded tumor tissue samples. The RNA is then extracted, and protein and DNA depleted from the RNA-containing sample. After analysis of the RNA concentration, RNA is reverse transcribed using gene specific primers followed by RT-PCR to provide for cDNA amplification products.
Design of Intron-Based PCR Primers and Probes
PCR primers and probes can be designed based upon exon or intron sequences present in the mRNA transcript of the gene of interest. Primer/probe design can be performed using publicly available software, such as the DNA BLAT software developed by Kent, W. J., Genome Res. 12(4):656-64 (2002), or by the BLAST software including its variations.
Where necessary or desired, repetitive sequences of the target sequence can be masked to mitigate non-specific signals. Exemplary tools to accomplish this include the Repeat Masker program available on-line through the Baylor College of Medicine, which screens DNA sequences against a library of repetitive elements and returns a query sequence in which the repetitive elements are masked. The masked intron sequences can then be used to design primer and probe sequences using any commercially or otherwise publicly available primer/probe design packages, such as Primer Express (Applied Biosystems); MGB assay-by-design (Applied Biosystems); Primer3 (Steve Rozen and Helen J. Skaletsky (2000) Primer3 on the WWW for general users and for biologist programmers. See S. Rrawetz, S. Misener, Bioinformatics Methods and Protocols: Methods in Molecular Biology, pp. 365-386 (Humana Press).
Other factors that can influence PCR primer design include primer length, melting temperature (Tm), and G/C content, specificity, complementary primer sequences, and 3′-end sequence. In general, optimal PCR primers are generally 17-30 bases in length, and contain about 20-80%, such as, for example, about 50-60% G+C bases, and exhibit Tm's between 50 and 80° C., e.g. about 50 to 70° C.
For further guidelines for PCR primer and probe design see, e.g. Dieffenbach, C W. et al, “General Concepts for PCR Primer Design” in: PCR Primer, A Laboratory Manual, Cold Spring Harbor Laboratory Press,. New York, 1995, pp. 133-155; Innis and Gelfand, “Optimization of PCRs” in: PCR Protocols, A Guide to Methods and Applications, CRC Press, London, 1994, pp. 5-11; and Plasterer, T. N. Primerselect: Primer and probe design. Methods Mol. Biol. 70:520-527 (1997), the entire disclosures of which are hereby expressly incorporated by reference.
Table A provides further information concerning the primer, probe, and amplicon sequences associated with the Examples disclosed herein.
MassARRAY® System
In MassARRAY-based methods, such as the exemplary method developed by Sequenom, Inc. (San Diego, Calif.) following the isolation of RNA and reverse transcription, the obtained cDNA is spiked with a synthetic DNA molecule (competitor), which matches the targeted cDNA region in all positions, except a single base, and serves as an internal standard. The cDNA/competitor mixture is PCR amplified and is subjected to a post-PCR shrimp alkaline phosphatase (SAP) enzyme treatment, which results in the dephosphorylation of the remaining nucleotides. After inactivarion of the alkaline phosphatase, the PCR products from the competitor and cDNA are subjected to primer extension, which generates distinct mass signals for the competitor- and cDNA-derives PCR products. After purification, these products are dispensed on a chip array, which is pre-loaded with components needed for analysis with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. The cDNA present in the reaction is then quantified by analyzing the ratios of the peak areas in the mass spectrum generated. For further details see, e.g. Ding and Cantor, Proc. Natl. Acad. Sci. USA 100:3059-3064 (2003).
Other PCR-Based Methods
Further PCR-based techniques that can find use in the methods disclosed herein include, for example, BeadArray® technology (Illumina, San Diego, Calif.; Oliphant et al., Discovery of Markers for Disease (Supplement to Biotechniques), June 2002; Ferguson et al., Analytical Chemistry 72:5618 (2000)); BeadsArray for Detection of Gene Expression® (BADGE), using the commercially available LuminexlOO LabMAP® system and multiple color-coded microspheres (Luminex Corp., Austin, Tex.) in a rapid assay for gene expression (Yang et al., Genome Res. 11:1888-1898 (2001)); and high coverage expression profiling (HiCEP) analysis (Fukumura et al., Nucl. Acids. Res. 31(16) e94 (2003).
Microarrays
Expression levels of a gene or microArray of interest can also be assessed using the microarray technique. In this method, polynucleotide sequences of interest (including cDNAs and oligonucleotides) are arrayed on a substrate. The arrayed sequences are then contacted under conditions suitable for specific hybridization with detectably labeled cDNA generated from RNA of a test sample. As in the RT-PCR method, the source of RNA typically is total RNA isolated from a tumor sample, and optionally from normal tissue of the same patient as an internal control or cell lines. RNA can be extracted, for example, from frozen or archived paraffin-embedded and fixed (e.g. formalin-fixed) tissue samples.
For example, PCR amplified inserts of cDNA clones of a gene to be assayed are applied to a substrate in a dense array. Usually at least 10,000 nucleotide sequences are applied to the substrate. For example, the microarrayed genes, immobilized on the microchip at 10,000 elements each, are suitable for hybridization under stringent conditions. Fluorescently labeled cDNA probes may be generated through incorporation of fluorescent nucleotides by reverse transcription of RNA extracted from tissues of interest. Labeled cDNA probes applied to the chip hybridize with specificity to each spot of DNA on the array. After washing under stringent conditions to remove non-specifically bound probes, the chip is scanned by confocal laser microscopy or by another detection method, such as a CCD camera. Quantitation of hybridization of each arrayed element allows for assessment of corresponding RNA abundance.
With dual color fluorescence, separately labeled cDNA probes generated from two sources of RNA are hybridized pair wise to the array. The relative abundance of the transcripts from the two sources corresponding to each specified gene is thus determined simultaneously. The miniaturized scale of the hybridization affords a convenient and rapid evaluation of the expression pattern for large numbers of genes. Such methods have been shown to have the sensitivity required to detect rare transcripts, which are expressed at a few copies per cell, and to reproducibly detect at least approximately two-fold differences in the expression levels (Schena et at, Proc. Natl. Acad. ScL USA 93(2):106-149 (1996)). Microarray analysis can be performed by commercially available equipment, following manufacturer's protocols, such as by using the Affymetrix GenChip® technology, or Incyte's microarray technology.
Serial Analysis of Gene Expression (SAGE)
Serial analysis of gene expression (SAGE) is a method that allows the simultaneous and quantitative analysis of a large number of gene transcripts, without the need of providing an individual hybridization probe for each transcript. First, a short sequence tag (about 10-14 bp) is generated that contains sufficient information to uniquely identify a transcript, provided that the tag is obtained from a unique position within each transcript. Then, many transcripts are linked together to form long serial molecules, that can be sequenced, revealing the identity of the multiple tags simultaneously. The expression pattern of any population of transcripts can be quantitatively evaluated by determining the abundance of individual tags, and identifying the gene corresponding to each tag. For more details see, e.g. Velculescu et al., Science 270:484-487 (1995); and Velculescu et al., Cell 88:243-51 (1997).
Gene Expression Analysis by Nucleic Acid Sequencing
Nucleic acid sequencing technologies are suitable methods for analysis of gene expression. The principle underlying these methods is that the number of times a cDNA sequence is detected in a sample is directly related to the relative expression of the RNA corresponding to that sequence. These methods are sometimes referred to by the term Digital Gene Expression (DGE) to reflect the discrete numeric property of the resulting data. Early methods applying this principle were Serial Analysis of Gene Expression (SAGE) and Massively Parallel Signature Sequencing (MPSS). See, e.g., S. Brenner, et al., Nature Biotechnology 18(6):630-634 (2000). More recently, the advent of “next-generation” sequencing technologies has made DGE simpler, higher throughput, and more affordable. As a result, more laboratories are able to utilize DGE to screen the expression of more genes in more individual patient samples than previously possible. See, e.g., J. Marioni, Genome Research 18(9):1509-1517 (2008); R. Morin, Genome Research 18(4):610-621 (2008); A. Mortazavi, Nature Methods 5(7):621-628 (2008); N. Cloonan, Nature Methods 5(7):613-619 (2008).
Isolating RNA from Body Fluids
Methods of isolating RNA for expression analysis from blood, plasma and serum (see, e.g., K. Enders, et al., Clin Chem 48,1647-53 (2002) (and references cited therein) and from urine (see, e.g., R. Boom, et al., J Clin Microbiol. 28, 495-503 (1990) and references cited therein) have been described.
Immunohistochemistry
Immunohistochemistry methods are also suitable for detecting the expression levels of genes and applied to the method disclosed herein. Antibodies (e.g., monoclonal antibodies) that specifically bind a gene product of a gene of interest can be used in such methods. The antibodies can be detected by direct labeling of the antibodies themselves, for example, with radioactive labels, fluorescent labels, hapten' labels such as, biotin, or an enzyme such as horse radish peroxidase or alkaline phosphatase. Alternatively, unlabeled primary antibody can be used in conjunction with a labeled secondary antibody specific for the primary antibody. Immunohistochemistry protocols and kits are well known in the art and are commercially available.
Proteomics
The term “proteome” is defined as the totality of the proteins present in a sample (e.g. tissue, organism, or cell culture) at a certain point of time. Proteomics includes, among other things, study of the global changes of protein expression in a sample (also referred to as “expression proteomics”). Proteomics typically includes the following steps: (1) separation of individual proteins in a sample by 2-D gel electrophoresis (2-D PAGE); (2) identification of the individual proteins recovered from the gel, e.g. my mass spectrometry or N-terminal sequencing, and (3) analysis of the data using bioinformatics.
General Description of the mRNA/microRNA Isolation, Purification and Amplification
The steps of a representative protocol for profiling gene expression using fixed, paraffin-embedded tissues as the RNA source, including mRNA or microRNA isolation, purification, primer extension and amplification are provided in various published journal articles. (See, e.g., T. E. Godfrey, et al,. J. Molec. Diagnostics 2: 84-91 (2000); K. Specht et al., Am. J. Pathol. 158: 419-29 (2001), M. Cronin, et al., Am J Pathol 164:35-42 (2004)). Briefly, a representative process starts with cutting a tissue sample section (e.g.about 10 μm thick sections of a paraffin-embedded tumor tissue sample). The RNA is then extracted, and protein and DNA are removed. After analysis of the RNA concentration, RNA repair is performed if desired. The sample can then be subjected to analysis, e.g., by reverse transcribed using gene specific promoters followed by RT-PCR.
Statistical Analysis of Expression Levels in Identification of Genes and MicroRNAs One skilled in the art will recognize that there are many statistical methods that may be used to determine whether there is a significant relationship between a parameter of interest (e.g., recurrence) and expression levels of a marker gene/microRNA as described here. In an exemplary embodiment, the present invention provides a stratified cohort sampling design (a form of case-control sampling) using tissue and data from prostate cancer patients. Selection of specimens was stratified by T stage (T1, T2), year cohort (<1993, ≥1993), and prostatectomy Gleason Score (low/intermediate, high). All patients with clinical recurrence were selected and a sample of patients who did not experience a clinical recurrence was selected. For each patient, up to two enriched tumor specimens and one normal-appearing tissue sample was assayed.
All hypothesis tests were reported using two-sided p-values. To investigate if there is a significant relationship of outcomes (clinical recurrence-free interval (cRFI), biochemical recurrence-free interval (bRFI), prostate cancer-specific survival (PCSS), and overall survival (OS)) with individual genes and/or microRNAs, demographic or clinical covariates Cox Proportional Hazards (PH) models using maximum weighted pseudo partial-likelihood estimators were used and p-values from Wald tests of the null hypothesis that the hazard ratio (HR) is one are reported. To investigate if there is a significant relationship between individual genes and/or microRNAs and Gleason pattern of a particular sample, ordinal logistic regression models using maximum weighted likelihood methods were used and p-values from Wald tests of the null hypothesis that the odds ratio (OR) is one are reported.
Coexpression Analysis The present disclosure provides a method to determine tumor stage based on the expression of staging genes, or genes that co-express with particular staging genes. To perform particular biological processes, genes often work together in a concerted way, i.e. they are co-expressed. Co-expressed gene groups identified for a disease process like cancer can serve as biomarkers for tumor status and disease progression. Such co-expressed genes can be assayed in lieu of, or in addition to, assaying of the staging gene with which they are co-expressed.
In an exemplary embodiment, the joint correlation of gene expression levels among prostate cancer specimens under study may be assessed. For this purpose, the correlation structures among genes and specimens may be examined through hierarchical cluster methods. This information may be used to confirm that genes that are known to be highly correlated in prostate cancer specimens cluster together as expected. Only genes exhibiting a nominally significant (unadjusted p<0.05) relationship with cRFI in the univariate Cox PH regression analysis will be included in these analyses.
One skilled in the art will recognize that many co-expression analysis methods now known or later developed will fall within the scope and spirit of the present invention. These methods may incorporate, for example, correlation coefficients, co-expression network analysis, clique analysis, etc., and may be based on expression data from RT-PCR, microarrays, sequencing, and other similar technologies. For example, gene expression clusters can be identified using pair-wise analysis of correlation based on Pearson or Spearman correlation coefficients. (See, e.g., Pearson K. and Lee A., Biometrika 2, 357 (1902); C. Spearman, Amer. J. Psychol 15:72-101 (1904); J. Myers, A. Well, Research Design and Statistical Analysis, p. 508 (2nd Ed., 2003).)
Normalization of Expression Levels The expression data used in the methods disclosed herein can be normalized. Normalization refers to a process to correct for (normalize away), for example, differences in the amount of RNA assayed and variability in the quality of the RNA used, to remove unwanted sources of systematic variation in Ct or Cp measurements, and the like. With respect to RT-PCR experiments involving archived fixed paraffin embedded tissue samples, sources of systematic variation are known to include the degree of RNA degradation relative to the age of the patient sample and the type of fixative used to store the sample. Other sources of systematic variation are attributable to laboratory processing conditions.
Assays can provide for normalization by incorporating the expression of certain normalizing genes, which do not significantly differ in expression levels under the relevant conditions. Exemplary normalization genes disclosed herein include housekeeping genes. (See, e.g., E. Eisenberg, et al., Trends in Genetics 19(7):362-365 (2003).) Normalization can be based on the mean or median signal (Ct or Cp) of all of the assayed genes or a large subset thereof (global normalization approach). In general, the normalizing genes, also referred to as reference genes should be genes that are known not to exhibit significantly different expression in prostate cancer as compared to non-cancerous prostate tissue, and are not significantly affected by various sample and process conditions, thus provide for normalizing away extraneous effects.
In exemplary embodiments, one or more of the following genes are used as references by which the mRNA or microRNA expression data is normalized: AAMP, ARF1, ATP5E, CLTC, GPS1, and PGK1. In another exemplary embodiment, one or more of the following microRNAs are used as references by which the expression data of microRNAs are normalized: hsa-miR-106a; hsa-miR-146b-5p; hsa-miR-191; hsa-miR-19b; and hsa-miR-92a. The calibrated weighted average CT or Cp measurements for each of the prognostic and predictive genes or microRNAs may be normalized relative to the mean of five or more reference genes or microRNAs.
Those skilled in the art will recognize that normalization may be achieved in numerous ways, and the techniques described above are intended only to be exemplary, not exhaustive.
Standardization of Expression Levels The expression data used in the methods disclosed herein can be standardized. Standardization refers to a process to effectively put all the genes or microRNAs on a comparable scale. This is performed because some genes or microRNAs will exhibit more variation (a broader range of expression) than others. Standardization is performed by dividing each expression value by its standard deviation across all samples for that gene or microRNA. Hazard ratios are then interpreted as the relative risk of recurrence per 1 standard deviation increase in expression.
Kits of the Invention The materials for use in the methods of the present invention are suited for preparation of kits produced in accordance with well-known procedures. The present disclosure thus provides kits comprising agents, which may include gene (or microRNA)-specific or gene (or microRNA)-selective probes and/or primers, for quantifying the expression of the disclosed genes or microRNAs for predicting prognostic outcome or response to treatment. Such kits may optionally contain reagents for the extraction of RNA from tumor samples, in particular fixed paraffin-embedded tissue samples and/or reagents for RNA amplification. In addition, the kits may optionally comprise the reagent(s) with an identifying description or label or instructions relating to their use in the methods of the present invention. The kits may comprise containers (including microliter plates suitable for use in an automated implementation of the method), each with one or more of the various materials or reagents (typically in concentrated form) utilized in the methods, including, for example, chromatographic columns, pre-fabricated microarrays, buffers, the appropriate nucleotide triphosphates (e.g., dATP, dCTP, dGTP and dTTP; or rATP, rCTP, rGTP and UTP), reverse transcriptase, DNA polymerase, RNA polymerase, and one or more probes and primers of the present invention (e.g., appropriate length poly(T) or random primers linked to a promoter reactive with the RNA polymerase). Mathematical algorithms used to estimate or quantify prognostic or predictive information are also properly potential components of kits.
Reports The methods of this invention, when practiced for commercial diagnostic purposes, generally produce a report or summary of information obtained from the herein-described methods. For example, a report may include information concerning expression levels of one or more genes and /or microRNAs, classification of the tumor or the patient's risk of recurrence, the patient's likely prognosis or risk classification, clinical and pathologic factors, and/or other information. The methods and reports of this invention can further include storing the report in a database. The method can create a record in a database for the subject and populate the record with data. The report may be a paper report, an auditory report, or an electronic record. The report may be displayed and/or stored on a computing device (e.g., handheld device, desktop computer, smart device, website, etc.). It is contemplated that the report is provided to a physician and/or the patient. The receiving of the report can further include establishing a network connection to a server computer that includes the data and report and requesting the data and report from the server computer.
Computer Program The values from the assays described above, such as expression data, can be calculated and stored manually. Alternatively, the above-described steps can be completely or partially performed by a computer program product. The present invention thus provides a computer program product including a computer readable storage medium having a computer program stored on it. The program can, when read by a computer, execute relevant calculations based on values obtained from analysis of one or more biological sample from an individual (e.g., gene expression levels, normalization, standardization, thresholding, and conversion of values from assays to a score and/or text or graphical depiction of tumor stage and related information). The computer program product has stored therein a computer program for performing the calculation.
The present disclosure provides systems for executing the program described above, which system generally includes: a) a central computing environment; b) an input device, operatively connected to the computing environment, to receive patient data, wherein the patient data can include, for example, expression level or other value obtained from an assay using a biological sample from the patient, or microarray data, as described in detail above; c) an output device, connected to the computing environment, to provide information to a user (e.g., medical personnel); and d) an algorithm executed by the central computing environment (e.g., a processor), where the algorithm is executed based on the data received by the input device, and wherein the algorithm calculates an expression score, thresholding, or other functions described herein. The methods provided by the present invention may also be automated in whole or in part.
All aspects of the present invention may also be practiced such that a limited number of additional genes and/or microRNAs that are co-expressed or functionally related with the disclosed genes, for example as evidenced by statistically meaningful Pearson and/or Spearman correlation coefficients, are included in a test in addition to and/or in place of disclosed genes.
Having described the invention, the same will be more readily understood through reference to the following Examples, which are provided by way of illustration, and are not intended to limit the invention in any way.
EXAMPLES Example 1 RNA Yield and Gene Expression Profiles in Prostate Cancer Biopsy Cores Clinical tools based on prostate needle core biopsies are needed to guide treatment planning at diagnosis for men with localized prostate cancer. Limiting tissue in needle core biopsy specimens poses significant challenges to the development of molecular diagnostic tests. This study examined RNA extraction yields and gene expression profiles using an RT-PCR assay to characterize RNA from manually micro-dissected fixed paraffin embedded (FPE) prostate cancer needle biopsy cores. It also investigated the association of RNA yields and gene expression profiles with Gleason score in these specimens.
Patients and Samples
This study determined the feasibility of gene expression profile analysis in prostate cancer needle core biopsies by evaluating the quantity and quality of RNA extracted from fixed paraffin-embedded (FPE) prostate cancer needle core biopsy specimens. Forty-eight (48) formalin-fixed blocks from prostate needle core biopsy specimens were used for this study. Classification of specimens was based on interpretation of the Gleason score (2005 Int'l Society of Urological Pathology Consensus Conference) and percentage tumor (<33%, 33-66%, >66%) involvement as assessed by pathologists.
TABLE 1
Distribution of cases
Gleason score ~<33% ~33-66% ~>66%
Category Tumor Tumor Tumor
Low (≤6) 5 5 6
Intermediate (7) 5 5 6
High (8, 9, 10) 5 5 6
Total 15 15 18
Assay Methods
Fourteen (14) serial 5 μm unstained sections from each FPE tissue block were included in the study. The first and last sections for each case were H&E stained and histologically reviewed to confirm the presence of tumor and for tumor enrichment by manual micro-dissection.
RNA from enriched tumor samples was extracted using a manual RNA extraction process. RNA was quantitated using the RiboGreen® assay and tested for the presence of genomic DNA contamination. Samples with sufficient RNA yield and free of genomic DNA tested for gene expression levels of a 24-gene panel of reference and cancer-related genes using quantitative RT-PCR. The expression was normalized to the average of 6 reference genes (AAMP, ARF1, ATP5E, CLTC, EEF1A1, and GPX1).
Statistical Methods
Descriptive statistics and graphical displays were used to summarize standard pathology metrics and gene expression, with stratification for Gleason Score category and percentage tumor involvement category. Ordinal logistic regression was used to evaluate the relationship between gene expression and Gleason Score category.
Results
The RNA yield per unit surface area ranged from 16 to 2406 ng/mm2. Higher RNA yield was observed in samples with higher percent tumor involvement (p=0.02) and higher Gleason score (p=0.01). RNA yield was sufficient (>200 ng) in 71% of cases to permit 96-well RT-PCR, with 87% of cases having >100 ng RNA yield. The study confirmed that gene expression from prostate biopsies, as measured by qRT-PCR, was comparable to FPET samples used in commercial molecular assays for breast cancer. In addition, it was observed that greater biopsy RNA yields are found with higher Gleason score and higher percent tumor involvement. Nine genes were identified as significantly associated with Gleason score (p<0.05) and there was a large dynamic range observed for many test genes.
Example 2 Gene Expression Analysis for Genes Associated with Prognosis in Prostate Cancer Patients and Samples
Approximately 2600 patients with clinical stage T1/T2 prostate cancer treated with radical prostatectomy (RP) at the Cleveland Clinic between 1987 and 2004 were identified. Patients were excluded from the study design if they received neo-adjuvant and/or adjuvant therapy, if pre-surgical PSA levels were missing, or if no tumor block was available from initial diagnosis. 127 patients with clinical recurrence and 374 patients without clinical recurrence after radical prostatectomy were randomly selected using a cohort sampling design. The specimens were stratified by T stage (T1, T2), year cohort (<1993, ≥1993), and prostatectomy Gleason score (low/intermediate, high). Of the 501 sampled patients, 51 were excluded for insufficient tumor; 7 were excluded due to clinical ineligibility; 2 were excluded due to poor quality of gene expression data; and 10 were excluded because primary Gleason pattern was unavailable. Thus, this gene expression study included tissue and data from 111 patients with clinical recurrence and 330 patients without clinical recurrence after radical prostatectomies performed between 1987 and 2004 for treatment of early stage (T1, T2) prostate cancer.
Two fixed paraffin embedded (FPE) tissue specimens were obtained from prostate tumor specimens in each patient. The sampling method (sampling method A or B) depended on whether the highest Gleason pattern is also the primary Gleason pattern. For each specimen selected, the invasive cancer cells were at least 5.0 mm in dimension, except in the instances of pattern 5, where 2.2 mm was accepted. Specimens were spatially distinct where possible.
TABLE 2
Sampling Methods
Sampling Method A Sampling Method B
For patients whose prostatectomy primary For patients whose prostatectomy primary
Gleason pattern is also the highest Gleason Gleason pattern is not the highest Gleason
pattern pattern
Specimen 1 (A1) = primary Gleason pattern Specimen 1 (B1) = highest Gleason pattern
Select and mark largest focus (greatest cross- Select highest Gleason pattern tissue from
sectional area) of primary Gleason pattern spatially distinct area from specimen B2, if
tissue. Invasive cancer area ≥ 5.0 mm. possible. Invasive cancer area at least 5.0
mm if selecting secondary pattern, at least
2.2 mm if selecting Gleason pattern 5.
Specimen 2 (A2) = secondary Gleason pattern Specimen 2 (B2) = primary Gleason pattern
Select and mark secondary Gleason pattern Select largest focus (greatest cross-sectional
tissue from spatially distinct area from area) of primary Gleason pattern tissue.
specimen A1. Invasive cancer area ≥ 5.0 mm. Invasive cancer area ≥ 5.0 mm.
Histologically normal appearing tissue (NAT) adjacent to the tumor specimen (also referred to in these Examples as “non-tumor tissue”) was also evaluated. Adjacent tissue was collected 3 mm from the tumor to 3 mm from the edge of the FPET block. NAT was preferentially sampled adjacent to the primary Gleason pattern. In cases where there was insufficient NAT adjacent to the primary Gleason pattern, then NAT was sampled adjacent to the secondary or highest Gleason pattern (A2 or B1) per the method set forth in Table 2. Six (6) 10 μm sections with beginning H&E at 5 μm and ending unstained slide at 5 μm were prepared from each fixed paraffin-embedded tumor (FPET) block included in the study. All cases were histologically reviewed and manually micro-dissected to yield two enriched tumor samples and, where possible, one normal tissue sample adjacent to the tumor specimen.
Assay Method
In this study, RT-PCR analysis was used to determine RNA expression levels for 738 genes and chromosomal rearrangements (e.g., TMPRSS2-ERG fusion or other ETS family genes) in prostate cancer tissue and surrounding NAT in patients with early-stage prostate cancer treated with radical prostatectomy.
The samples were quantified using the RiboGreen assay and a subset tested for presence of genomic DNA contamination. Samples were taken into reverse transcription (RT) and quantitative polymerase chain reaction (qPCR). All analyses were conducted on reference-normalized gene expression levels using the average of the of replicate well crossing point (CP) values for the 6 reference genes (AAMP, ARF1, ATP5E, CLTC, GPS1, PGK1).
Statistical Analysis and Results
Primary statistical analyses involved 111 patients with clinical recurrence and 330 patients without clinical recurrence after radical prostatectomy for early-stage prostate cancer stratified by T-stage (T1, T2), year cohort (<1993, ≥1993), and prostatectomy Gleason score (low/intermediate, high). Gleason score categories are defined as follows: low (Gleason score≤6), intermediate (Gleason score=7), and high (Gleason score≥8). A patient was included in a specified analysis if at least one sample for that patient was evaluable. Unless otherwise stated, all hypothesis tests were reported using two-sided p-values. The method of Storey was applied to the resulting set of p-values to control the false discovery rate (FDR) at 20%. J. Storey, R. Tibshirani, Estimating the Positive False Discovery Rate Under Dependence, with Applications to DNA Microarrays, Dept. of Statistics, Stanford Univ. (2001).
Analysis of gene expression and recurrence-free interval was based on univariate Cox Proportional Hazards (PH) models using maximum weighted pseudo-partial-likelihood estimators for each evaluable gene in the gene list (727 test genes and 5 reference genes). P-values were generated using Wald tests of the null hypothesis that the hazard ratio (HR) is one. Both unadjusted p-values and the q-value (smallest FDR at which the hypothesis test in question is rejected) were reported. Un-adjusted p-values <0.05 were considered statistically significant. Since two tumor specimens were selected for each patient, this analysis was performed using the 2 specimens from each patient as follows: (1) analysis using the primary Gleason pattern specimen from each patient (Specimens A1 and B2 as described in Table 2); (2) analysis using the highest Gleason pattern specimen from each patient (Specimens A1 and B1 as described in Table 2).
Analysis of gene expression and Gleason pattern (3, 4, 5) was based on univariate ordinal logistic regression models using weighted maximum likelihood estimators for each gene in the gene list (727 test genes and 5 reference genes). P-values were generated using a Wald test of the null hypothesis that the odds ratio (OR) is one. Both unadjusted p-values and the q-value (smallest FDR at which the hypothesis test in question is rejected) were reported. Un-adjusted p-values<0.05 were considered statistically significant. Since two tumor specimens were selected for each patient, this analysis was performed using the 2 specimens from each patient as follows: (1) analysis using the primary Gleason pattern specimen from each patient (Specimens A1 and B2 as described in Table 2); (2) analysis using the highest Gleason pattern specimen from each patient (Specimens A1 and B1 as described in Table 2).
It was determined whether there is a significant relationship between cRFI and selected demographic, clinical, and pathology variables, including age, race, clinical tumor stage, pathologic tumor stage, location of selected tumor specimens within the prostate (peripheral versus transitional zone), PSA at the time of surgery, overall Gleason score from the radical prostatectomy, year of surgery, and specimen Gleason pattern. Separately for each demographic or clinical variable, the relationship between the clinical covariate and cRFI was modeled using univariate Cox PH regression using weighted pseudo partial-likelihood estimators and a p-value was generated using Wald's test of the null hypothesis that the hazard ratio (HR) is one. Covariates with unadjusted p-values<0.2 may have been included in the covariate-adjusted analyses.
It was determined whether there was a significant relationship between each of the individual cancer-related genes and cRFI after controlling for important demographic and clinical covariates. Separately for each gene, the relationship between gene expression and cRFI was modeled using multivariate Cox PH regression using weighted pseudo partial-likelihood estimators including important demographic and clinical variables as covariates. The independent contribution of gene expression to the prediction of cRFI was tested by generating a p-value from a Wald test using a model that included clinical covariates for each nodule (specimens as defined in Table 2). Un-adjusted p-values<0.05 were considered statistically significant.
Tables 3A and 3B provide genes significantly associated (p<0.05), positively or negatively, with Gleason pattern in the primary and/or highest Gleason pattern. Increased expression of genes in Table 3A is positively associated with higher Gleason score, while increased expression of genes in Table 3B are negatively associated with higher Gleason score.
TABLE 3A
Gene significantly (p < 0.05) associated with Gleason pattern
for all specimens in the primary Gleason pattern or highest
Gleason pattern odds ratio (OR) > 1.0 (Increased expression
is positively associated with higher Gleason Score)
Table 3A Primary Pattern Highest Pattern
Official Symbol OR p-value OR p-value
ALCAM 1.73 <.001 1.36 0.009
ANLN 1.35 0.027
APOC1 1.47 0.005 1.61 <.001
APOE 1.87 <.001 2.15 <.001
ASAP2 1.53 0.005
ASPN 2.62 <.001 2.13 <.001
ATP5E 1.35 0.035
AURKA 1.44 0.010
AURKB 1.59 <.001 1.56 <.001
BAX 1.43 0.006
BGN 2.58 <.001 2.82 <.001
BIRC5 1.45 0.003 1.79 <.001
BMP6 2.37 <.001 1.68 <.001
BMPR1B 1.58 0.002
BRCA2 1.45 0.013
BUB1 1.73 <.001 1.57 <.001
CACNA1D 1.31 0.045 1.31 0.033
CADPS 1.30 0.023
CCNB1 1.43 0.023
CCNE2 1.52 0.003 1.32 0.035
CD276 2.20 <.001 1.83 <.001
CD68 1.36 0.022
CDC20 1.69 <.001 1.95 <.001
CDC6 1.38 0.024 1.46 <.001
CDH11 1.30 0.029
CDKN2B 1.55 0.001 1.33 0.023
CDKN2C 1.62 <.001 1.52 <.001
CDKN3 1.39 0.010 1.50 0.002
CENPF 1.96 <.001 1.71 <.001
CHRAC1 1.34 0.022
CLDN3 1.37 0.029
COL1A1 2.23 <.001 2.22 <.001
COL1A2 1.42 0.005
COL3A1 1.90 <.001 2.13 <.001
COL8A1 1.88 <.001 2.35 <.001
CRISP3 1.33 0.040 1.26 0.050
CTHRC1 2.01 <.001 1.61 <.001
CTNND2 1.48 0.007 1.37 0.011
DAPK1 1.44 0.014
DIAPH1 1.34 0.032 1.79 <.001
DIO2 1.56 0.001
DLL4 1.38 0.026 1.53 <.001
ECE1 1.54 0.012 1.40 0.012
ENY2 1.35 0.046 1.35 0.012
EZH2 1.39 0.040
F2R 2.37 <.001 2.60 <.001
FAM49B 1.57 0.002 1.33 0.025
FAP 2.36 <.001 1.89 <.001
FCGR3A 2.10 <.001 1.83 <.001
GNPTAB 1.78 <.001 1.54 <.001
GSK3B 1.39 0.018
HRAS 1.62 0.003
HSD17B4 2.91 <.001 1.57 <.001
HSPA8 1.48 0.012 1.34 0.023
IFI30 1.64 <.001 1.45 0.013
IGFBP3 1.29 0.037
IL11 1.52 0.001 1.31 0.036
INHBA 2.55 <.001 2.30 <.001
ITGA4 1.35 0.028
JAG1 1.68 <.001 1.40 0.005
KCNN2 1.50 0.004
KCTD12 1.38 0.012
KHDRBS3 1.85 <.001 1.72 <.001
KIF4A 1.50 0.010 1.50 <.001
KLK14 1.49 0.001 1.35 <.001
KPNA2 1.68 0.004 1.65 0.001
KRT2 1.33 0.022
KRT75 1.27 0.028
LAMC1 1.44 0.029
LAPTM5 1.36 0.025 1.31 0.042
LTBP2 1.42 0.023 1.66 <.001
MANF 1.34 0.019
MAOA 1.55 0.003 1.50 <.001
MAP3K5 1.55 0.006 1.44 0.001
MDK 1.47 0.013 1.29 0.041
MDM2 1.31 0.026
MELK 1.64 <.001 1.64 <.001
MMP11 2.33 <.001 1.66 <.001
MYBL2 1.41 0.007 1.54 <.001
MYO6 1.32 0.017
NETO2 1.36 0.018
NOX4 1.84 <.001 1.73 <.001
NPM1 1.68 0.001
NRIP3 1.36 0.009
NRP1 1.80 0.001 1.36 0.019
OSM 1.33 0.046
PATE1 1.38 0.032
PECAM1 1.38 0.021 1.31 0.035
PGD 1.56 0.010
PLK1 1.51 0.004 1.49 0.002
PLOD2 1.29 0.027
POSTN 1.70 0.047 1.55 0.006
PPP3CA 1.38 0.037 1.37 0.006
PTK6 1.45 0.007 1.53 <.001
PTTG1 1.51 <.001
RAB31 1.31 0.030
RAD21 2.05 <.001 1.38 0.020
RAD51 1.46 0.002 1.26 0.035
RAF1 1.46 0.017
RALBP1 1.37 0.043
RHOC 1.33 0.021
ROBO2 1.52 0.003 1.41 0.006
RRM2 1.77 <.001 1.50 <.001
SAT1 1.67 0.002 1.61 <.001
SDC1 1.66 0.001 1.46 0.014
SEC14L1 1.53 0.003 1.62 <.001
SESN3 1.76 <.001 1.45 <.001
SFRP4 2.69 <.001 2.03 <.001
SHMT2 1.69 0.007 1.45 0.003
SKIL 1.46 0.005
SOX4 1.42 0.016 1.27 0.031
SPARC 1.40 0.024 1.55 <.001
SPINK1 1.29 0.002
SPP1 1.51 0.002 1.80 <.001
TFDP1 1.48 0.014
THBS2 1.87 <.001 1.65 <.001
THY1 1.58 0.003 1.64 <.001
TK1 1.79 <.001 1.42 0.001
TOP2A 2.30 <.001 2.01 <.001
TPD52 1.95 <.001 1.30 0.037
TPX2 2.12 <.001 1.86 <.001
TYMP 1.36 0.020
TYMS 1.39 0.012 1.31 0.036
UBE2C 1.66 <.001 1.65 <.001
UBE2T 1.59 <.001 1.33 0.017
UGDH 1.28 0.049
UGT2B15 1.46 0.001 1.25 0.045
UHRF1 1.95 <.001 1.62 <.001
VDR 1.43 0.010 1.39 0.018
WNT5A 1.54 0.001 1.44 0.013
TABLE 3B
Gene significantly (p < 0.05) associated with Gleason pattern for all
specimens in the primary Gleason pattern or highest Gleason
pattern odds ratio (OR) <1.0 (Increased expression is negatively
associated with higher Gleason score)
Table 3B Primary Pattern Highest Pattern
Official Symbol OR p-value OR p-value
ABCA5 0.78 0.041
ABCG2 0.65 0.001 0.72 0.012
ACOX2 0.44 <.001 0.53 <.001
ADH5 0.45 <.001 0.42 <.001
AFAP1 0.79 0.038
AIG1 0.77 0.024
AKAP1 0.63 0.002
AKR1C1 0.66 0.003 0.63 <.001
AKT3 0.68 0.006 0.77 0.010
ALDH1A2 0.28 <.001 0.33 <.001
ALKBH3 0.77 0.040 0.77 0.029
AMPD3 0.67 0.007
ANPEP 0.68 0.008 0.59 <.001
ANXA2 0.72 0.018
APC 0.69 0.002
AXIN2 0.46 <.001 0.54 <.001
AZGP1 0.52 <.001 0.53 <.001
BIK 0.69 0.006 0.73 0.003
BIN1 0.43 <.001 0.61 <.001
BTG3 0.79 0.030
BTRC 0.48 <.001 0.62 <.001
C7 0.37 <.001 0.55 <.001
CADM1 0.56 <.001 0.69 0.001
CAV1 0.58 0.002 0.70 0.009
CAV2 0.65 0.029
CCNH 0.67 0.006 0.77 0.048
CD164 0.59 0.003 0.57 <.001
CDC25B 0.77 0.035
CDH1 0.66 <.001
CDK2 0.71 0.003
CDKN1C 0.58 <.001 0.57 <.001
CDS2 0.69 0.002
CHN1 0.66 0.002
COL6A1 0.44 <.001 0.66 <.001
COL6A3 0.66 0.006
CSRP1 0.42 0.006
CTGF 0.74 0.043
CTNNA1 0.70 <.001 0.83 0.018
CTNNB1 0.70 0.019
CTNND1 0.75 0.028
CUL1 0.74 0.011
CXCL12 0.54 <.001 0.74 0.006
CYP3A5 0.52 <.001 0.66 0.003
CYR61 0.64 0.004 0.68 0.005
DDR2 0.57 0.002 0.73 0.004
DES 0.34 <.001 0.58 <.001
DLGAP1 0.54 <.001 0.62 <.001
DNM3 0.67 0.004
DPP4 0.41 <.001 0.53 <.001
DPT 0.28 <.001 0.48 <.001
DUSP1 0.59 <.001 0.63 <.001
EDNRA 0.64 0.004 0.74 0.008
EGF 0.71 0.012
EGR1 0.59 <.001 0.67 0.009
EGR3 0.72 0.026 0.71 0.025
EIF5 0.76 0.025
ELK4 0.58 0.001 0.70 0.008
ENPP2 0.66 0.002 0.70 0.005
EPHA3 0.65 0.006
EPHB2 0.60 <.001 0.78 0.023
EPHB4 0.75 0.046 0.73 0.006
ERBB3 0.76 0.040 0.75 0.013
ERBB4 0.74 0.023
ERCC1 0.63 <.001 0.77 0.016
FAAH 0.67 0.003 0.71 0.010
FAM107A 0.35 <.001 0.59 <.001
FAM13C 0.37 <.001 0.48 <.001
FAS 0.73 0.019 0.72 0.008
FGF10 0.53 <.001 0.58 <.001
FGF7 0.52 <.001 0.59 <.001
FGFR2 0.60 <.001 0.59 <.001
FKBP5 0.70 0.039 0.68 0.003
FLNA 0.39 <.001 0.56 <.001
FLNC 0.33 <.001 0.52 <.001
FOS 0.58 <.001 0.66 0.005
FOXO1 0.57 <.001 0.67 <.001
FOXQ1 0.74 0.023
GADD45B 0.62 0.002 0.71 0.010
GHR 0.62 0.002 0.72 0.009
GNRH1 0.74 0.049 0.75 0.026
GPM6B 0.48 <.001 0.68 <.001
GPS1 0.68 0.003
GSN 0.46 <.001 0.77 0.027
GSTM1 0.44 <.001 0.62 <.001
GSTM2 0.29 <.001 0.49 <.001
HGD 0.77 0.020
HIRIP3 0.75 0.034
HK1 0.48 <.001 0.66 0.001
HLF 0.42 <.001 0.55 <.001
HNF1B 0.67 0.006 0.74 0.010
HPS1 0.66 0.001 0.65 <.001
HSP90AB1 0.75 0.042
HSPA5 0.70 0.011
HSPB2 0.52 <.001 0.70 0.004
IGF1 0.35 <.001 0.59 <.001
IGF2 0.48 <.001 0.70 0.005
IGFBP2 0.61 <.001 0.77 0.044
IGFBP5 0.63 <.001
IGFBP6 0.45 <.001 0.64 <.001
IL6ST 0.55 0.004 0.63 <.001
ILK 0.40 <.001 0.57 <.001
ING5 0.56 <.001 0.78 0.033
ITGA1 0.56 0.004 0.61 <.001
ITGA3 0.78 0.035
ITGA5 0.71 0.019 0.75 0.017
ITGA7 0.37 <.001 0.52 <.001
ITGB3 0.63 0.003 0.70 0.005
ITPR1 0.46 <.001 0.64 <.001
ITPR3 0.70 0.013
ITSN1 0.62 0.001
JUN 0.48 <.001 0.60 <.001
JUNB 0.72 0.025
KIT 0.51 <.001 0.68 0.007
KLC1 0.58 <.001
KLK1 0.69 0.028 0.66 0.003
KLK2 0.60 <.001
KLK3 0.63 <.001 0.69 0.012
KRT15 0.56 <.001 0.60 <.001
KRT18 0.74 0.034
KRT5 0.64 <.001 0.62 <.001
LAMA4 0.47 <.001 0.73 0.010
LAMB3 0.73 0.018 0.69 0.003
LGALS3 0.59 0.003 0.54 <.001
LIG3 0.75 0.044
MAP3K7 0.66 0.003 0.79 0.031
MCM3 0.73 0.013 0.80 0.034
MGMT 0.61 0.001 0.71 0.007
MGST1 0.75 0.017
MLXIP 0.70 0.013
MMP2 0.57 <.001 0.72 0.010
MMP7 0.69 0.009
MPPED2 0.70 0.009 0.59 <.001
MSH6 0.78 0.046
MTA1 0.69 0.007
MTSS1 0.55 <.001 0.54 <.001
MYBPC1 0.45 <.001 0.45 <.001
NCAM1 0.51 <.001 0.65 <.001
NCAPD3 0.42 <.001 0.53 <.001
NCOR2 0.68 0.002
NDUFS5 0.66 0.001 0.70 0.013
NEXN 0.48 <.001 0.62 <.001
NFAT5 0.55 <.001 0.67 0.001
NFKBIA 0.79 0.048
NRG1 0.58 0.001 0.62 0.001
OLFML3 0.42 <.001 0.58 <.001
OMD 0.67 0.004 0.71 0.004
OR51E2 0.65 <.001 0.76 0.007
PAGE4 0.27 <.001 0.46 <.001
PCA3 0.68 0.004
PCDHGB7 0.70 0.025 0.65 <.001
PGF 0.62 0.001
PGR 0.63 0.028
PHTF2 0.69 0.033
PLP2 0.54 <.001 0.71 0.003
PPAP2B 0.41 <.001 0.54 <.001
PPP1R12A 0.48 <.001 0.60 <.001
PRIMA1 0.62 0.003 0.65 <.001
PRKAR1B 0.70 0.009
PRKAR2B 0.79 0.038
PRKCA 0.37 <.001 0.55 <.001
PRKCB 0.47 <.001 0.56 <.001
PTCH1 0.70 0.021
PTEN 0.66 0.010 0.64 <.001
PTGER3 0.76 0.015
PTGS2 0.70 0.013 0.68 0.005
PTH1R 0.48 <.001
PTK2B 0.67 0.014 0.69 0.002
PYCARD 0.72 0.023
RAB27A 0.76 0.017
RAGE 0.77 0.040 0.57 <.001
RARB 0.66 0.002 0.69 0.002
RECK 0.65 <.001
RHOA 0.73 0.043
RHOB 0.61 0.005 0.62 <.001
RND3 0.63 0.006 0.66 <.001
SDHC 0.69 0.002
SEC23A 0.61 <.001 0.74 0.010
SEMA3A 0.49 <.001 0.55 <.001
SERPINA3 0.70 0.034 0.75 0.020
SH3RF2 0.33 <.001 0.42 <.001
SLC22A3 0.23 <.001 0.37 <.001
SMAD4 0.33 <.001 0.39 <.001
SMARCC2 0.62 0.003 0.74 0.008
SMO 0.53 <.001 0.73 0.009
SORBS1 0.40 <.001 0.55 <.001
SPARCL1 0.42 <.001 0.63 <.001
SRD5A2 0.28 <.001 0.37 <.001
ST5 0.52 <.001 0.63 <.001
STAT5A 0.60 <.001 0.75 0.020
STAT5B 0.54 <.001 0.65 <.001
STS 0.78 0.035
SUMO1 0.75 0.017 0.71 0.002
SVIL 0.45 <.001 0.62 <.001
TARP 0.72 0.017
TGFB1I1 0.37 <.001 0.53 <.001
TGFB2 0.61 0.025 0.59 <.001
TGFB3 0.46 <.001 0.60 <.001
TIMP2 0.62 0.001
TIMP3 0.55 <.001 0.76 0.019
TMPRSS2 0.71 0.014
TNF 0.65 0.010
TNFRSF10A 0.71 0.014 0.74 0.010
TNFRSF10B 0.74 0.030 0.73 0.016
TNFSF10 0.69 0.004
TP53 0.73 0.011
TP63 0.62 <.001 0.68 0.003
TPM1 0.43 <.001 0.47 <.001
TPM2 0.30 <.001 0.47 <.001
TPP2 0.58 <.001 0.69 0.001
TRA2A 0.71 0.006
TRAF3IP2 0.50 <.001 0.63 <.001
TRO 0.40 <.001 0.59 <.001
TRPC6 0.73 0.030
TRPV6 0.80 0.047
VCL 0.44 <.001 0.55 <.001
VEGFB 0.73 0.029
VIM 0.72 0.013
VTI1B 0.78 0.046
WDR19 0.65 <.001
WFDC1 0.50 <.001 0.72 0.010
YY1 0.75 0.045
ZFHX3 0.52 <.001 0.54 <.001
ZFP36 0.65 0.004 0.69 0.012
ZNF827 0.59 <.001 0.69 0.004
To identify genes associated with recurrence (cRFI, bRFI) in the primary and the highest Gleason pattern, each of 727 genes were analyzed in univariate models using specimens A1 and B2 (see Table 2, above). Tables 4A and 4B provide genes that were associated, positively or negatively, with cRFI and/or bRFI in the primary and/or highest Gleason pattern. Increased expression of genes in Table 4A is negatively associated with good prognosis, while increased expression of genes in Table 4B is positively associated with good prognosis.
TABLE 4A
Genes significantly (p < 0.05) associated with cRFI or bRFI in the primary
Gleason pattern or highest Gleason pattern with hazard ratio (HR) > 1.0
(increased expression is negatively associated with good prognosis)
cRFI cRFI bRFI bRFI
Table 4A Primary Highest Primary Highest
Official Pattern Pattern Pattern Pattern
Symbol HR p-value HR p-value HR p-value HR p-value
AKR1C3 1.304 0.022 1.312 0.013
ANLN 1.379 0.002 1.579 <.001 1.465 <.001 1.623 <.001
AQP2 1.184 0.027 1.276 <.001
ASAP2 1.442 0.006
ASPN 2.272 <.001 2.106 <.001 1.861 <.001 1.895 <.001
ATP5E 1.414 0.013 1.538 <.001
BAG5 1.263 0.044
BAX 1.332 0.026 1.327 0.012 1.438 0.002
BGN 1.947 <.001 2.061 <.001 1.339 0.017
BIRC5 1.497 <.001 1.567 <.001 1.478 <.001 1.575 <.001
BMP6 1.705 <.001 2.016 <.001 1.418 0.004 1.541 <.001
BMPR1B 1.401 0.013 1.325 0.016
BRCA2 1.259 0.007
BUB1 1.411 <.001 1.435 <.001 1.352 <.001 1.242 0.002
CADPS 1.387 0.009 1.294 0.027
CCNB1 1.296 0.016 1.376 0.002
CCNE2 1.468 <.001 1.649 <.001 1.729 <.001 1.563 <.001
CD276 1.678 <.001 1.832 <.001 1.581 <.001 1.385 0.002
CDC20 1.547 <.001 1.671 <.001 1.446 <.001 1.540 <.001
CDC6 1.400 0.003 1.290 0.030 1.403 0.002 1.276 0.019
CDH7 1.403 0.003 1.413 0.002
CDKN2B 1.569 <.001 1.752 <.001 1.333 0.017 1.347 0.006
CDKN2C 1.612 <.001 1.780 <.001 1.323 0.005 1.335 0.004
CDKN3 1.384 <.001 1.255 0.024 1.285 0.003 1.216 0.028
CENPF 1.578 <.001 1.692 <.001 1.740 <.001 1.705 <.001
CKS2 1.390 0.007 1.418 0.005 1.291 0.018
CLTC 1.368 0.045
COL1A1 1.873 <.001 2.103 <.001 1.491 <.001 1.472 <.001
COL1A2 1.462 0.001
COL3A1 1.827 <.001 2.005 <.001 1.302 0.012 1.298 0.018
COL4A1 1.490 0.002 1.613 <.001
COL8A1 1.692 <.001 1.926 <.001 1.307 0.013 1.317 0.010
CRISP3 1.425 0.001 1.467 <.001 1.242 0.045
CTHRC1 1.505 0.002 2.025 <.001 1.425 0.003 1.369 0.005
CTNND2 1.412 0.003
CXCR4 1.312 0.023 1.355 0.008
DDIT4 1.543 <.001 1.763 <.001
DYNLL1 1.290 0.039 1.201 0.004
EIF3H 1.428 0.012
ENY2 1.361 0.014 1.392 0.008 1.371 0.001
EZH2 1.311 0.010
F2R 1.773 <.001 1.695 <.001 1.495 <.001 1.277 0.018
FADD 1.292 0.018
FAM171B 1.285 0.036
FAP 1.455 0.004 1.560 0.001 1.298 0.022 1.274 0.038
FASN 1.263 0.035
FCGR3A 1.654 <.001 1.253 0.033 1.350 0.007
FGF5 1.219 0.030
GNPTAB 1.388 0.007 1.503 0.003 1.355 0.005 1.434 0.002
GPR68 1.361 0.008
GREM1 1.470 0.003 1.716 <.001 1.421 0.003 1.316 0.017
HDAC1 1.290 0.025
HDAC9 1.395 0.012
HRAS 1.424 0.006 1.447 0.020
HSD17B4 1.342 0.019 1.282 0.026 1.569 <.001 1.390 0.002
HSPA8 1.290 0.034
IGFBP3 1.333 0.022 1.442 0.003 1.253 0.040 1.323 0.005
INHBA 2.368 <.001 2.765 <.001 1.466 0.002 1.671 <.001
JAG1 1.359 0.006 1.367 0.005 1.259 0.024
KCNN2 1.361 0.011 1.413 0.005 1.312 0.017 1.281 0.030
KHDRBS3 1.387 0.006 1.601 <.001 1.573 <.001 1.353 0.006
KIAA0196 1.249 0.037
KIF4A 1.212 0.016 1.149 0.040 1.278 0.003
KLK14 1.167 0.023 1.180 0.007
KPNA2 1.425 0.009 1.353 0.005 1.305 0.019
KRT75 1.164 0.028
LAMA3 1.327 0.011
LAMB1 1.347 0.019
LAMC1 1.555 0.001 1.310 0.030 1.349 0.014
LIMS1 1.275 0.022
LOX 1.358 0.003 1.410 <.001
LTBP2 1.396 0.009 1.656 <.001 1.278 0.022
LUM 1.315 0.021
MANF 1.660 <.001 1.323 0.011
MCM2 1.345 0.011 1.387 0.014
MCM6 1.307 0.023 1.352 0.008 1.244 0.039
MELK 1.293 0.014 1.401 <.001 1.501 <.001 1.256 0.012
MMP11 1.680 <.001 1.474 <.001 1.489 <.001 1.257 0.030
MRPL13 1.260 0.025
MSH2 1.295 0.027
MYBL2 1.664 <.001 1.670 <.001 1.399 <.001 1.431 <.001
MYO6 1.301 0.033
NETO2 1.412 0.004 1.302 0.027 1.298 0.009
NFKB1 1.236 0.050
NOX4 1.492 <.001 1.507 0.001 1.555 <.001 1.262 0.019
NPM1 1.287 0.036
NRIP3 1.219 0.031 1.218 0.018
NRP1 1.482 0.002 1.245 0.041
OLFML2B 1.362 0.015
OR51E1 1.531 <.001 1.488 0.003
PAK6 1.269 0.033
PATE1 1.308 <.001 1.332 <.001 1.164 0.044
PCNA 1.278 0.020
PEX10 1.436 0.005 1.393 0.009
PGD 1.298 0.048 1.579 <.001
PGK1 1.274 0.023 1.262 0.009
PLA2G7 1.315 0.011 1.346 0.005
PLAU 1.319 0.010
PLK1 1.309 0.021 1.563 <.001 1.410 0.002 1.372 0.003
PLOD2 1.284 0.019 1.272 0.014 1.332 0.005
POSTN 1.599 <.001 1.514 0.002 1.391 0.005
PPP3CA 1.402 0.007 1.316 0.018
PSMD13 1.278 0.040 1.297 0.033 1.279 0.017 1.373 0.004
PTK6 1.640 <.001 1.932 <.001 1.369 0.001 1.406 <.001
PTTG1 1.409 <.001 1.510 <.001 1.347 0.001 1.558 <.001
RAD21 1.315 0.035 1.402 0.004 1.589 <.001 1.439 <.001
RAF1 1.503 0.002
RALA 1.521 0.004 1.403 0.007 1.563 <.001 1.229 0.040
RALBP1 1.277 0.033
RGS7 1.154 0.015 1.266 0.010
RRM1 1.570 0.001 1.602 <.001
RRM2 1.368 <.001 1.289 0.004 1.396 <.001 1.230 0.015
SAT1 1.482 0.016 1.403 0.030
SDC1 1.340 0.018 1.396 0.018
SEC14L1 1.260 0.048 1.360 0.002
SESN3 1.485 <.001 1.631 <.001 1.232 0.047 1.292 0.014
SFRP4 1.800 <.001 1.814 <.001 1.496 <.001 1.289 0.027
SHMT2 1.807 <.001 1.658 <.001 1.673 <.001 1.548 <.001
SKIL 1.327 0.008
SLC25A21 1.398 0.001 1.285 0.018
SOX4 1.286 0.020 1.280 0.030
SPARC 1.539 <.001 1.842 <.001 1.269 0.026
SPP1 1.322 0.022
SQLE 1.359 0.020 1.270 0.036
STMN1 1.402 0.007 1.446 0.005 1.279 0.031
SULF1 1.587 <.001
TAF2 1.273 0.027
TFDP1 1.328 0.021 1.400 0.005 1.416 0.001
THBS2 1.812 <.001 1.960 <.001 1.320 0.012 1.256 0.038
THY1 1.362 0.020 1.662 <.001
TK1 1.251 0.011 1.377 <.001 1.401 <.001
TOP2A 1.670 <.001 1.920 <.001 1.869 <.001 1.927 <.001
TPD52 1.324 0.011 1.366 0.002 1.351 0.005
TPX2 1.884 <.001 2.154 <.001 1.874 <.001 1.794 <.001
UAP1 1.244 0.044
UBE2C 1.403 <.001 1.541 <.001 1.306 0.002 1.323 <.001
UBE2T 1.667 <.001 1.282 0.023 1.502 <.001 1.298 0.005
UGT2B15 1.295 0.001 1.275 0.002
UGT2B17 1.294 0.025
UHRF1 1.454 <.001 1.531 <.001 1.257 0.029
VCPIP1 1.390 0.009 1.414 0.004 1.294 0.021 1.283 0.021
WNT5A 1.274 0.038 1.298 0.020
XIAP 1.464 0.006
ZMYND8 1.277 0.048
ZWINT 1.259 0.047
TABLE 4B
Genes significantly (p < 0.05) associated with cRFI or bRFI in the primary
Gleason pattern or highest Gleason pattern with hazard ratio (HR) < 1.0
(increased expression is positively associated with good prognosis)
cRFI cRFI bRFI bRFI
Table 4B Primary Highest Primary Highest
Official Pattern Pattern Pattern Pattern
Symbol HR p-value HR p-value HR p-value HR p-value
AAMP 0.564 <.001 0.571 <.001 0.764 0.037 0.786 0.034
ABCA5 0.755 <.001 0.695 <.001 0.800 0.006
ABCB1 0.777 0.026
ABCG2 0.788 0.033 0.784 0.040 0.803 0.018 0.750 0.004
ABHD2 0.734 0.011
ACE 0.782 0.048
ACOX2 0.639 <.001 0.631 <.001 0.713 <.001 0.716 0.002
ADH5 0.625 <.001 0.637 <.001 0.753 0.026
AKAP1 0.764 0.006 0.800 0.005 0.837 0.046
AKR1C1 0.773 0.033 0.802 0.032
AKT1 0.714 0.005
AKT3 0.811 0.015 0.809 0.021
ALDH1A2 0.606 <.001 0.498 <.001 0.613 <.001 0.624 <.001
AMPD3 0.793 0.024
ANPEP 0.584 <.001 0.493 <.001
ANXA2 0.753 0.013 0.781 0.036 0.762 0.008 0.795 0.032
APRT 0.758 0.026 0.780 0.044 0.746 0.008
ATXN1 0.673 0.001 0.776 0.029 0.809 0.031 0.812 0.043
AXIN2 0.674 <.001 0.571 <.001 0.776 0.005 0.757 0.005
AZGP1 0.585 <.001 0.652 <.001 0.664 <.001 0.746 <.001
BAD 0.765 0.023
BCL2 0.788 0.033 0.778 0.036
BDKRB1 0.728 0.039
BIK 0.712 0.005
BIN1 0.607 <.001 0.724 0.002 0.726 <.001 0.834 0.034
BTG3 0.847 0.034
BTRC 0.688 0.001 0.713 0.003
C7 0.589 <.001 0.639 <.001 0.629 <.001 0.691 <.001
CADM1 0.546 <.001 0.529 <.001 0.743 0.008 0.769 0.015
CASP1 0.769 0.014 0.799 0.028 0.799 0.010 0.815 0.018
CAV1 0.736 0.011 0.711 0.005 0.675 <.001 0.743 0.006
CAV2 0.636 0.010 0.648 0.012 0.685 0.012
CCL2 0.759 0.029 0.764 0.024
CCNH 0.689 <.001 0.700 <.001
CD164 0.664 <.001 0.651 <.001
CD1A 0.687 0.004
CD44 0.545 <.001 0.600 <.001 0.788 0.018 0.799 0.023
CD82 0.771 0.009 0.748 0.004
CDC25B 0.755 0.006 0.817 0.025
CDK14 0.845 0.043
CDK2 0.819 0.032
CDK3 0.733 0.005 0.772 0.006 0.838 0.017
CDKN1A 0.766 0.041
CDKN1C 0.662 <.001 0.712 0.002 0.693 <.001 0.761 0.009
CHN1 0.788 0.036
COL6A1 0.608 <.001 0.767 0.013 0.706 <.001 0.775 0.007
CSF1 0.626 <.001 0.709 0.003
CSK 0.837 0.029
CSRP1 0.793 0.024 0.782 0.019
CTNNB1 0.898 0.042 0.885 <.001
CTSB 0.701 0.004 0.713 0.007 0.715 0.002 0.803 0.038
CTSK 0.815 0.042
CXCL12 0.652 <.001 0.802 0.044 0.711 0.001
CYP3A5 0.463 <.001 0.436 <.001 0.727 0.003
CYR61 0.652 0.002 0.676 0.002
DAP 0.761 0.026 0.775 0.025 0.802 0.048
DARC 0.725 0.005 0.792 0.032
DDR2 0.719 0.001 0.763 0.008
DES 0.619 <.001 0.737 0.005 0.638 <.001 0.793 0.017
DHRS9 0.642 0.003
DHX9 0.888 <.001
DLC1 0.710 0.007 0.715 0.009
DLGAP1 0.613 <.001 0.551 <.001 0.779 0.049
DNM3 0.679 <.001 0.812 0.037
DPP4 0.591 <.001 0.613 <.001 0.761 0.003
DPT 0.613 <.001 0.576 <.001 0.647 <.001 0.677 <.001
DUSP1 0.662 0.001 0.665 0.001 0.785 0.024
DUSP6 0.713 0.005 0.668 0.002
EDNRA 0.702 0.002 0.779 0.036
EGF 0.738 0.028
EGR1 0.569 <.001 0.577 <.001 0.782 0.022
EGR3 0.601 <.001 0.619 <.001 0.800 0.038
EIF2S3 0.756 0.015
EIF5 0.776 0.023 0.787 0.028
ELK4 0.628 <.001 0.658 <.001
EPHA2 0.720 0.011 0.663 0.004
EPHA3 0.727 0.003 0.772 0.005
ERBB2 0.786 0.019 0.738 0.003 0.815 0.041
ERBB3 0.728 0.002 0.711 0.002 0.828 0.043 0.813 0.023
ERCC1 0.771 0.023 0.725 0.007 0.806 0.049 0.704 0.002
EREG 0.754 0.016 0.777 0.034
ESR2 0.731 0.026
FAAH 0.708 0.004 0.758 0.012 0.784 0.031 0.774 0.007
FAM107A 0.517 <.001 0.576 <.001 0.642 <.001 0.656 <.001
FAM13C 0.568 <.001 0.526 <.001 0.739 0.002 0.639 <.001
FAS 0.755 0.014
FASLG 0.706 0.021
FGF10 0.653 <.001 0.685 <.001 0.766 0.022
FGF17 0.746 0.023 0.781 0.015 0.805 0.028
FGF7 0.794 0.030 0.820 0.037 0.811 0.040
FGFR2 0.683 <.001 0.686 <.001 0.674 <.001 0.703 <.001
FKBP5 0.676 0.001
FLNA 0.653 <.001 0.741 0.010 0.682 <.001 0.771 0.016
FLNC 0.751 0.029 0.779 0.047 0.663 <.001 0.725 <.001
FLT1 0.799 0.044
FOS 0.566 <.001 0.543 <.001 0.757 0.006
FOXO1 0.816 0.039 0.798 0.023
FOXQ1 0.753 0.017 0.757 0.024 0.804 0.018
FYN 0.779 0.031
GADD45B 0.590 <.001 0.619 <.001
GDF15 0.759 0.019 0.794 0.048
GHR 0.702 0.005 0.630 <.001 0.673 <.001 0.590 <.001
GNRH1 0.742 0.014
GPM6B 0.653 <.001 0.633 <.001 0.696 <.001 0.768 0.007
GSN 0.570 <.001 0.697 0.001 0.697 <.001 0.758 0.005
GSTM1 0.612 <.001 0.588 <.001 0.718 <.001 0.801 0.020
GSTM2 0.540 <.001 0.630 <.001 0.602 <.001 0.706 <.001
HGD 0.796 0.020 0.736 0.002
HIRIP3 0.753 0.011 0.824 0.050
HK1 0.684 <.001 0.683 <.001 0.799 0.011 0.804 0.014
HLA-G 0.726 0.022
HLF 0.555 <.001 0.582 <.001 0.703 <.001 0.702 <.001
HNF1B 0.690 <.001 0.585 <.001
HPS1 0.744 0.003 0.784 0.020 0.836 0.047
HSD3B2 0.733 0.016
HSP90AB1 0.801 0.036
HSPA5 0.776 0.034
HSPB1 0.813 0.020
HSPB2 0.762 0.037 0.699 0.002 0.783 0.034
HSPG2 0.794 0.044
ICAM1 0.743 0.024 0.768 0.040
IER3 0.686 0.002 0.663 <.001
IFIT1 0.649 <.001 0.761 0.026
IGF1 0.634 <.001 0.537 <.001 0.696 <.001 0.688 <.001
IGF2 0.732 0.004
IGFBP2 0.548 <.001 0.620 <.001
IGFBP5 0.681 <.001
IGFBP6 0.577 <.001 0.675 <.001
IL1B 0.712 0.005 0.742 0.009
IL6 0.763 0.028
IL6R 0.791 0.039
IL6ST 0.585 <.001 0.639 <.001 0.730 0.002 0.768 0.006
IL8 0.624 <.001 0.662 0.001
ILK 0.712 0.009 0.728 0.012 0.790 0.047 0.790 0.042
ING5 0.625 <.001 0.658 <.001 0.728 0.002
ITGA5 0.728 0.006 0.803 0.039
ITGA6 0.779 0.007 0.775 0.006
ITGA7 0.584 <.001 0.700 0.001 0.656 <.001 0.786 0.014
ITGAD 0.657 0.020
ITGB4 0.718 0.007 0.689 <.001 0.818 0.041
ITGB5 0.801 0.050
ITPR1 0.707 0.001
JUN 0.556 <.001 0.574 <.001 0.754 0.008
JUNB 0.730 0.017 0.715 0.010
KIT 0.644 0.004 0.705 0.019 0.605 <.001 0.659 0.001
KLC1 0.692 0.003 0.774 0.024 0.747 0.008
KLF6 0.770 0.032 0.776 0.039
KLK1 0.646 <.001 0.652 0.001 0.784 0.037
KLK10 0.716 0.006
KLK2 0.647 <.001 0.628 <.001 0.786 0.009
KLK3 0.706 <.001 0.748 <.001 0.845 0.018
KRT1 0.734 0.024
KRT15 0.627 <.001 0.526 <.001 0.704 <.001 0.782 0.029
KRT18 0.624 <.001 0.617 <.001 0.738 0.005 0.760 0.005
KRT5 0.640 <.001 0.550 <.001 0.740 <.001 0.798 0.023
KRT8 0.716 0.006 0.744 0.008
L1CAM 0.738 0.021 0.692 0.009 0.761 0.036
LAG3 0.741 0.013 0.729 0.011
LAMA4 0.686 0.011 0.592 0.003
LAMA5 0.786 0.025
LAMB3 0.661 <.001 0.617 <.001 0.734 <.001
LGALS3 0.618 <.001 0.702 0.001 0.734 0.001 0.793 0.012
LIG3 0.705 0.008 0.615 <.001
LRP1 0.786 0.050 0.795 0.023 0.770 0.009
MAP3K7 0.789 0.003
MGMT 0.632 <.001 0.693 <.001
MICA 0.781 0.014 0.653 <.001 0.833 0.043
MPPED2 0.655 <.001 0.597 <.001 0.719 <.001 0.759 0.006
MSH6 0.793 0.015
MTSS1 0.613 <.001 0.746 0.008
MVP 0.792 0.028 0.795 0.045 0.819 0.023
MYBPC1 0.648 <.001 0.496 <.001 0.701 <.001 0.629 <.001
NCAM1 0.773 0.015
NCAPD3 0.574 <.001 0.463 <.001 0.679 <.001 0.640 <.001
NEXN 0.701 0.002 0.791 0.035 0.725 0.002 0.781 0.016
NFAT5 0.515 <.001 0.586 <.001 0.785 0.017
NFATC2 0.753 0.023
NFKBIA 0.778 0.037
NRG1 0.644 0.004 0.696 0.017 0.698 0.012
OAZ1 0.777 0.034 0.775 0.022
OLFML3 0.621 <.001 0.720 0.001 0.600 <.001 0.626 <.001
OMD 0.706 0.003
OR51E2 0.820 0.037 0.798 0.027
PAGE4 0.549 <.001 0.613 <.001 0.542 <.001 0.628 <.001
PCA3 0.684 <.001 0.635 <.001
PCDHGB7 0.790 0.045 0.725 0.002 0.664 <.001
PGF 0.753 0.017
PGR 0.740 0.021 0.728 0.018
PIK3CG 0.803 0.024
PLAUR 0.778 0.035
PLG 0.728 0.028
PPAP2B 0.575 <.001 0.629 <.001 0.643 <.001 0.699 <.001
PPP1R12A 0.647 <.001 0.683 0.002 0.782 0.023 0.784 0.030
PRIMA1 0.626 <.001 0.658 <.001 0.703 0.002 0.724 0.003
PRKCA 0.642 <.001 0.799 0.029 0.677 0.001 0.776 0.006
PRKCB 0.675 0.001 0.648 <.001 0.747 0.006
PROM1 0.603 0.018 0.659 0.014 0.493 0.008
PTCH1 0.680 0.001 0.753 0.010 0.789 0.018
PTEN 0.732 0.002 0.747 0.005 0.744 <.001 0.765 0.002
PTGS2 0.596 <.001 0.610 <.001
PTH1R 0.767 0.042 0.775 0.028 0.788 0.047
PTHLH 0.617 0.002 0.726 0.025 0.668 0.002 0.718 0.007
PTK2B 0.744 0.003 0.679 <.001 0.766 0.002 0.726 <.001
PTPN1 0.760 0.020 0.780 0.042
PYCARD 0.748 0.012
RAB27A 0.708 0.004
RAB30 0.755 0.008
RAGE 0.817 0.048
RAP1B 0.818 0.050
RARB 0.757 0.007 0.677 <.001 0.789 0.007 0.746 0.003
RASSF1 0.816 0.035
RHOB 0.725 0.009 0.676 0.001 0.793 0.039
RLN1 0.742 0.033 0.762 0.040
RND3 0.636 <.001 0.647 <.001
RNF114 0.749 0.011
SDC2 0.721 0.004
SDHC 0.725 0.003 0.727 0.006
SEMA3A 0.757 0.024 0.721 0.010
SERPINA3 0.716 0.008 0.660 0.001
SERPINB5 0.747 0.031 0.616 0.002
SH3RF2 0.577 <.001 0.458 <.001 0.702 <.001 0.640 <.001
SLC22A3 0.565 <.001 0.540 <.001 0.747 0.004 0.756 0.007
SMAD4 0.546 <.001 0.573 <.001 0.636 <.001 0.627 <.001
SMARCD1 0.718 <.001 0.775 0.017
SMO 0.793 0.029 0.754 0.021 0.718 0.003
SOD1 0.757 0.049 0.707 0.006
SORBS1 0.645 <.001 0.716 0.003 0.693 <.001 0.784 0.025
SPARCL1 0.821 0.028 0.829 0.014 0.781 0.030
SPDEF 0.778 <.001
SPINT1 0.732 0.009 0.842 0.026
SRC 0.647 <.001 0.632 <.001
SRD5A1 0.813 0.040
SRD5A2 0.489 <.001 0.533 <.001 0.544 <.001 0.611 <.001
ST5 0.713 0.002 0.783 0.011 0.725 <.001 0.827 0.025
STAT3 0.773 0.037 0.759 0.035
STAT5A 0.695 <.001 0.719 0.002 0.806 0.020 0.783 0.008
STAT5B 0.633 <.001 0.655 <.001 0.814 0.028
SUMO1 0.790 0.015
SVIL 0.659 <.001 0.713 0.002 0.711 0.002 0.779 0.010
TARP 0.800 0.040
TBP 0.761 0.010
TFF3 0.734 0.010 0.659 <.001
TGFB1I1 0.618 <.001 0.693 0.002 0.637 <.001 0.719 0.004
TGFB2 0.679 <.001 0.747 0.005 0.805 0.030
TGFB3 0.791 0.037
TGFBR2 0.778 0.035
TIMP3 0.751 0.011
TMPRSS2 0.745 0.003 0.708 <.001
TNF 0.670 0.013 0.697 0.015
TNFRSF10A 0.780 0.018 0.752 0.006 0.817 0.032
TNFRSF10B 0.576 <.001 0.655 <.001 0.766 0.004 0.778 0.002
TNFRSF18 0.648 0.016 0.759 0.034
TNFSF10 0.653 <.001 0.667 0.004
TP53 0.729 0.003
TP63 0.759 0.016 0.636 <.001 0.698 <.001 0.712 0.001
TPM1 0.778 0.048 0.743 0.012 0.783 0.032 0.811 0.046
TPM2 0.578 <.001 0.634 <.001 0.611 <.001 0.710 0.001
TPP2 0.775 0.037
TRAF3IP2 0.722 0.002 0.690 <.001 0.792 0.021 0.823 0.049
TRO 0.744 0.003 0.725 0.003 0.765 0.002 0.821 0.041
TUBB2A 0.639 <.001 0.625 <.001
TYMP 0.786 0.039
VCL 0.594 <.001 0.657 0.001 0.682 <.001
VEGFA 0.762 0.024
VEGFB 0.795 0.037
VIM 0.739 0.009 0.791 0.021
WDR19 0.776 0.015
WFDC1 0.746 <.001
YY1 0.683 0.001 0.728 0.002
ZFHX3 0.684 <.001 0.661 <.001 0.801 0.010 0.762 0.001
ZFP36 0.605 <.001 0.579 <.001 0.815 0.043
ZNF827 0.624 <.001 0.730 0.007 0.738 0.004
Tables 5A and 5B provide genes that were significantly associated (p<0.05), positively or negatively, with recurrence (cRFI, bRFI) after adjusting for AUA risk group in the primary and/or highest Gleason pattern. Increased expression of genes in Table 5A is negatively associated with good prognosis, while increased expression of genes in Table 5B is positively associated with good prognosis.
TABLE 5A
Gene significantly (p < 0.05) associated with cRFI or bRFI after
adjustment for AUA risk group in the primary Gleason pattern or highest
Gleason pattern with hazard ratio (HR) > 1.0 (increased expression
negatively associated with good prognosis)
cRFI cRFI bRFI bRFI
Table 5A Primary Highest Primary Highest
Official Pattern Pattern Pattern Pattern
Symbol HR p-value HR p-value HR p-value HR p-value
AKR1C3 1.315 0.018 1.283 0.024
ALOX12 1.198 0.024
ANLN 1.406 <.001 1.519 <.001 1.485 <.001 1.632 <.001
AQP2 1.209 <.001 1.302 <.001
ASAP2 1.582 <.001 1.333 0.011 1.307 0.019
ASPN 1.872 <.001 1.741 <.001 1.638 <.001 1.691 <.001
ATP5E 1.309 0.042 1.369 0.012
BAG5 1.291 0.044
BAX 1.298 0.025 1.420 0.004
BGN 1.746 <.001 1.755 <.001
BIRC5 1.480 <.001 1.470 <.001 1.419 <.001 1.503 <.001
BMP6 1.536 <.001 1.815 <.001 1.294 0.033 1.429 0.001
BRCA2 1.184 0.037
BUB1 1.288 0.001 1.391 <.001 1.254 <.001 1.189 0.018
CACNA1D 1.313 0.029
CADPS 1.358 0.007 1.267 0.022
CASP3 1.251 0.037
CCNB1 1.261 0.033 1.318 0.005
CCNE2 1.345 0.005 1.438 <.001 1.606 <.001 1.426 <.001
CD276 1.482 0.002 1.668 <.001 1.451 <.001 1.302 0.011
CDC20 1.417 <.001 1.547 <.001 1.355 <.001 1.446 <.001
CDC6 1.340 0.011 1.265 0.046 1.367 0.002 1.272 0.025
CDH7 1.402 0.003 1.409 0.002
CDKN2B 1.553 <.001 1.746 <.001 1.340 0.014 1.369 0.006
CDKN2C 1.411 <.001 1.604 <.001 1.220 0.033
CDKN3 1.296 0.004 1.226 0.015
CENPF 1.434 0.002 1.570 <.001 1.633 <.001 1.610 <.001
CKS2 1.419 0.008 1.374 0.022 1.380 0.004
COL1A1 1.677 <.001 1.809 <.001 1.401 <.001 1.352 0.003
COL1A2 1.373 0.010
COL3A1 1.669 <.001 1.781 <.001 1.249 0.024 1.234 0.047
COL4A1 1.475 0.002 1.513 0.002
COL8A1 1.506 0.001 1.691 <.001
CRISP3 1.406 0.004 1.471 <.001
CTHRC1 1.426 0.009 1.793 <.001 1.311 0.019
CTNND2 1.462 <.001
DDIT4 1.478 0.003 1.783 <.001 1.236 0.039
DYNLL1 1.431 0.002 1.193 0.004
EIF3H 1.372 0.027
ENY2 1.325 0.023 1.270 0.017
ERG 1.303 0.041
EZH2 1.254 0.049
F2R 1.540 0.002 1.448 0.006 1.286 0.023
FADD 1.235 0.041 1.404 <.001
FAP 1.386 0.015 1.440 0.008 1.253 0.048
FASN 1.303 0.028
FCGR3A 1.439 0.011 1.262 0.045
FGF5 1.289 0.006
GNPTAB 1.290 0.033 1.369 0.022 1.285 0.018 1.355 0.008
GPR68 1.396 0.005
GREM1 1.341 0.022 1.502 0.003 1.366 0.006
HDAC1 1.329 0.016
HDAC9 1.378 0.012
HRAS 1.465 0.006
HSD17B4 1.442 <.001 1.245 0.028
IGFBP3 1.366 0.019 1.302 0.011
INHBA 2.000 <.001 2.336 <.001 1.486 0.002
JAG1 1.251 0.039
KCNN2 1.347 0.020 1.524 <.001 1.312 0.023 1.346 0.011
KHDRBS3 1.500 0.001 1.426 0.001 1.267 0.032
KIAA0196 1.272 0.028
KIF4A 1.199 0.022 1.262 0.004
KPNA2 1.252 0.016
LAMA3 1.332 0.004 1.356 0.010
LAMB1 1.317 0.028
LAMC1 1.516 0.003 1.302 0.040 1.397 0.007
LIMS1 1.261 0.027
LOX 1.265 0.016 1.372 0.001
LTBP2 1.477 0.002
LUM 1.321 0.020
MANF 1.647 <.001 1.284 0.027
MCM2 1.372 0.003 1.302 0.032
MCM3 1.269 0.047
MCM6 1.276 0.033 1.245 0.037
MELK 1.294 0.005 1.394 <.001
MKI67 1.253 0.028 1.246 0.029
MMP11 1.557 <.001 1.290 0.035 1.357 0.005
MRPL13 1.275 0.003
MSH2 1.355 0.009
MYBL2 1.497 <.001 1.509 <.001 1.304 0.003 1.292 0.007
MYO6 1.367 0.010
NDRG1 1.270 0.042 1.314 0.025
NEK2 1.338 0.020 1.269 0.026
NETO2 1.434 0.004 1.303 0.033 1.283 0.012
NOX4 1.413 0.006 1.308 0.037 1.444 <.001
NRIP3 1.171 0.026
NRP1 1.372 0.020
ODC1 1.450 <.001
OR51E1 1.559 <.001 1.413 0.008
PAK6 1.233 0.047
PATE1 1.262 <.001 1.375 <.001 1.143 0.034 1.191 0.036
PCNA 1.227 0.033 1.318 0.003
PEX10 1.517 <.001 1.500 0.001
PGD 1.363 0.028 1.316 0.039 1.652 <.001
PGK1 1.224 0.034 1.206 0.024
PIM1 1.205 0.042
PLA2G7 1.298 0.018 1.358 0.005
PLAU 1.242 0.032
PLK1 1.464 0.001 1.299 0.018 1.275 0.031
PLOD2 1.206 0.039 1.261 0.025
POSTN 1.558 0.001 1.356 0.022 1.363 0.009
PPP3CA 1.445 0.002
PSMD13 1.301 0.017 1.411 0.003
PTK2 1.318 0.031
PTK6 1.582 <.001 1.894 <.001 1.290 0.011 1.354 0.003
PTTG1 1.319 0.004 1.430 <.001 1.271 0.006 1.492 <.001
RAD21 1.278 0.028 1.435 0.004 1.326 0.008
RAF1 1.504 <.001
RALA 1.374 0.028 1.459 0.001
RGS7 1.203 0.031
RRM1 1.535 0.001 1.525 <.001
RRM2 1.302 0.003 1.197 0.047 1.342 <.001
SAT1 1.374 0.043
SDC1 1.344 0.011 1.473 0.008
SEC14L1 1.297 0.006
SESN3 1.337 0.002 1.495 <.001 1.223 0.038
SFRP4 1.610 <.001 1.542 0.002 1.370 0.009
SHMT2 1.567 0.001 1.522 <.001 1.485 0.001 1.370 <.001
SKIL 1.303 0.008
SLC25A21 1.287 0.020 1.306 0.017
SLC44A1 1.308 0.045
SNRPB2 1.304 0.018
SOX4 1.252 0.031
SPARC 1.445 0.004 1.706 <.001 1.269 0.026
SPP1 1.376 0.016
SQLE 1.417 0.007 1.262 0.035
STAT1 1.209 0.029
STMN1 1.315 0.029
SULF1 1.504 0.001
TAF2 1.252 0.048 1.301 0.019
TFDP1 1.395 0.010 1.424 0.002
THBS2 1.716 <.001 1.719 <.001
THY1 1.343 0.035 1.575 0.001
TK1 1.320 <.001 1.304 <.001
TOP2A 1.464 0.001 1.688 <.001 1.715 <.001 1.761 <.001
TPD52 1.286 0.006 1.258 0.023
TPX2 1.644 <.001 1.964 <.001 1.699 <.001 1.754 <.001
TYMS 1.315 0.014
UBE2C 1.270 0.019 1.558 <.001 1.205 0.027 1.333 <.001
UBE2G1 1.302 0.041
UBE2T 1.451 <.001 1.309 0.003
UGT2B15 1.222 0.025
UHRF1 1.370 0.003 1.520 <.001 1.247 0.020
VCPIP1 1.332 0.015
VTI1B 1.237 0.036
XIAP 1.486 0.008
ZMYND8 1.408 0.007
ZNF3 1.284 0.018
ZWINT 1.289 0.028
TABLE 5B
Genes significantly (p < 0.05) associated with cRFI or bRFI after
adjustment for AUA risk group in the primary Gleason pattern or
highest Gleason pattern with hazard ratio (HR) < 1.0 (increased
expression is positively associated with good prognosis)
cRFI cRFI bRFI
Primary Highest Primary bRFI
Table 5B Pattern Pattern Pattern Highest
Official p- p- p- Pattern
Symbol HR value HR value HR value HR p-value
AAMP 0.535 <.001 0.581 <.001 0.700 0.002 0.759 0.006
ABCA5 0.798 0.007 0.745 0.002 0.841 0.037
ABCC1 0.800 0.044
ABCC4 0.787 0.022
ABHD2 0.768 0.023
ACOX2 0.678 0.002 0.749 0.027 0.759 0.004
ADH5 0.645 <.001 0.672 0.001
AGTR1 0.780 0.030
AKAP1 0.815 0.045 0.758 <.001
AKT1 0.732 0.010
ALDH1A2 0.646 <.001 0.548 <.001 0.671 <.001 0.713 0.001
ANPEP 0.641 <.001 0.535 <.001
ANXA2 0.772 0.035 0.804 0.046
ATXN1 0.654 <.001 0.754 0.020 0.797 0.017
AURKA 0.788 0.030
AXIN2 0.744 0.005 0.655 <.001
AZGP1 0.656 <.001 0.676 <.001 0.754 0.001 0.791 0.004
BAD 0.700 0.004
BIN1 0.650 <.001 0.764 0.013 0.803 0.015
BTG3 0.836 0.025
BTRC 0.730 0.005
C7 0.617 <.001 0.680 <.001 0.667 <.001 0.755 0.005
CADM1 0.559 <.001 0.566 <.001 0.772 0.020 0.802 0.046
CASP1 0.781 0.030 0.779 0.021 0.818 0.027 0.828 0.036
CAV1 0.775 0.034
CAV2 0.677 0.019
CCL2 0.752 0.023
CCNH 0.679 <.001 0.682 <.001
CD164 0.721 0.002 0.724 0.005
CD1A 0.710 0.014
CD44 0.591 <.001 0.642 <.001
CD82 0.779 0.021 0.771 0.024
CDC25B 0.778 0.035 0.818 0.023
CDK14 0.788 0.011
CDK3 0.752 0.012 0.779 0.005 0.841 0.020
CDKN1A 0.770 0.049 0.712 0.014
CDKN1C 0.684 <.001 0.697 <.001
CHN1 0.772 0.031
COL6A1 0.648 <.001 0.807 0.046 0.768 0.004
CSF1 0.621 <.001 0.671 0.001
CTNNB1 0.905 0.008
CTSB 0.754 0.030 0.716 0.011 0.756 0.014
CXCL12 0.641 <.001 0.796 0.038 0.708 <.001
CYP3A5 0.503 <.001 0.528 <.001 0.791 0.028
CYR61 0.639 0.001 0.659 0.001 0.797 0.048
DARC 0.707 0.004
DDR2 0.750 0.011
DES 0.657 <.001 0.758 0.022 0.699 <.001
DHRS9 0.625 0.002
DHX9 0.846 <.001
DIAPH1 0.682 0.007 0.723 0.008 0.780 0.026
DLC1 0.703 0.005 0.702 0.008
DLGAP1 0.703 0.008 0.636 <.001
DNM3 0.701 0.001 0.817 0.042
DPP4 0.686 <.001 0.716 0.001
DPT 0.636 <.001 0.633 <.001 0.709 0.006 0.773 0.024
DUSP1 0.683 0.006 0.679 0.003
DUSP6 0.694 0.003 0.605 <.001
EDN1 0.773 0.031
EDNRA 0.716 0.007
EGR1 0.575 <.001 0.575 <.001 0.771 0.014
EGR3 0.633 0.002 0.643 <.001 0.792 0.025
EIF4E 0.722 0.002
ELK4 0.710 0.009 0.759 0.027
ENPP2 0.786 0.039
EPHA2 0.593 0.001
EPHA3 0.739 0.006 0.802 0.020
ERBB2 0.753 0.007
ERBB3 0.753 0.009 0.753 0.015
ERCC1 0.727 0.001
EREG 0.722 0.012 0.769 0.040
ESR1 0.742 0.015
FABP5 0.756 0.032
FAM107A 0.524 <.001 0.579 <.001 0.688 <.001 0.699 0.001
FAM13C 0.639 <.001 0.601 <.001 0.810 0.019 0.709 <.001
FAS 0.770 0.033
FASLG 0.716 0.028 0.683 0.017
FGF10 0.798 0.045
FGF17 0.718 0.018 0.793 0.024 0.790 0.024
FGFR2 0.739 0.007 0.783 0.038 0.740 0.004
FGFR4 0.746 0.050
FKBP5 0.689 0.003
FLNA 0.701 0.006 0.766 0.029 0.768 0.037
FLNC 0.755 <.001 0.820 0.022
FLT1 0.729 0.008
FOS 0.572 <.001 0.536 <.001 0.750 0.005
FOXQ1 0.778 0.033 0.820 0.018
FYN 0.708 0.006
GADD45B 0.577 <.001 0.589 <.001
GDF15 0.757 0.013 0.743 0.006
GHR 0.712 0.004 0.679 0.001
GNRH1 0.791 0.048
GPM6B 0.675 <.001 0.660 <.001 0.735 <.001 0.823 0.049
GSK3B 0.783 0.042
GSN 0.587 <.001 0.705 0.002 0.745 0.004 0.796 0.021
GSTM1 0.686 0.001 0.631 <.001 0.807 0.018
GSTM2 0.607 <.001 0.683 <.001 0.679 <.001 0.800 0.027
HIRIP3 0.692 <.001 0.782 0.007
HK1 0.724 0.002 0.718 0.002
HLF 0.580 <.001 0.571 <.001 0.759 0.008 0.750 0.004
HNF1B 0.669 <.001
HPS1 0.764 0.008
HSD17B10 0.802 0.045
HSD17B2 0.723 0.048
HSD3B2 0.709 0.010
HSP90AB1 0.780 0.034 0.809 0.041
HSPA5 0.738 0.017
HSPB1 0.770 0.006 0.801 0.032
HSPB2 0.788 0.035
ICAM1 0.728 0.015 0.716 0.010
IER3 0.735 0.016 0.637 <.001 0.802 0.035
IFIT1 0.647 <.001 0.755 0.029
IGF1 0.675 <.001 0.603 <.001 0.762 0.006 0.770 0.030
IGF2 0.761 0.011
IGFBP2 0.601 <.001 0.605 <.001
IGFBP5 0.702 <.001
IGFBP6 0.628 <.001 0.726 0.003
IL1B 0.676 0.002 0.716 0.004
IL6 0.688 0.005 0.766 0.044
IL6R 0.786 0.036
IL6ST 0.618 <.001 0.639 <.001 0.785 0.027 0.813 0.042
IL8 0.635 <.001 0.628 <.001
ILK 0.734 0.018 0.753 0.026
ING5 0.684 <.001 0.681 <.001 0.756 0.006
ITGA4 0.778 0.040
ITGA5 0.762 0.026
ITGA6 0.811 0.038
ITGA7 0.592 <.001 0.715 0.006 0.710 0.002
ITGAD 0.576 0.006
ITGB4 0.693 0.003
ITPR1 0.789 0.029
JUN 0.572 <.001 0.581 <.001 0.777 0.019
JUNB 0.732 0.030 0.707 0.016
KCTD12 0.758 0.036
KIT 0.691 0.009 0.738 0.028
KLC1 0.741 0.024 0.781 0.024
KLF6 0.733 0.018 0.727 0.014
KLK1 0.744 0.028
KLK2 0.697 0.002 0.679 <.001
KLK3 0.725 <.001 0.715 <.001 0.841 0.023
KRT15 0.660 <.001 0.577 <.001 0.750 0.002
KRT18 0.623 <.001 0.642 <.001 0.702 <.001 0.760 0.006
KRT2 0.740 0.044
KRT5 0.674 <.001 0.588 <.001 0.769 0.005
KRT8 0.768 0.034
L1CAM 0.737 0.036
LAG3 0.711 0.013 0.748 0.029
LAMA4 0.649 0.009
LAMB3 0.709 0.002 0.684 0.006 0.768 0.006
LGALS3 0.652 <.001 0.752 0.015 0.805 0.028
LIG3 0.728 0.016 0.667 <.001
LRP1 0.811 0.043
MDM2 0.788 0.033
MGMT 0.645 <.001 0.766 0.015
MICA 0.796 0.043 0.676 <.001
MPPED2 0.675 <.001 0.616 <.001 0.750 0.006
MRC1 0.788 0.028
MTSS1 0.654 <.001 0.793 0.036
MYBPC1 0.706 <.001 0.534 <.001 0.773 0.004 0.692 <.001
NCAPD3 0.658 <.001 0.566 <.001 0.753 0.011 0.733 0.009
NCOR1 0.838 0.045
NEXN 0.748 0.025 0.785 0.020
NFAT5 0.531 <.001 0.626 <.001
NFATC2 0.759 0.024
OAZ1 0.766 0.024
OLFML3 0.648 <.001 0.748 0.005 0.639 <.001 0.675 <.001
OR51E2 0.823 0.034
PAGE4 0.599 <.001 0.698 0.002 0.606 <.001 0.726 <.001
PCA3 0.705 <.001 0.647 <.001
PCDHGB7 0.712 <.001
PGF 0.790 0.039
PLG 0.764 0.048
PLP2 0.766 0.037
PPAP2B 0.589 <.001 0.647 <.001 0.691 <.001 0.765 0.013
PPP1R12A 0.673 0.001 0.677 0.001 0.807 0.045
PRIMA1 0.622 <.001 0.712 0.008 0.740 0.013
PRKCA 0.637 <.001 0.694 <.001
PRKCB 0.741 0.020 0.664 <.001
PROM1 0.599 0.017 0.527 0.042 0.610 0.006 0.420 0.002
PTCH1 0.752 0.027 0.762 0.011
PTEN 0.779 0.011 0.802 0.030 0.788 0.009
PTGS2 0.639 <.001 0.606 <.001
PTHLH 0.632 0.007 0.739 0.043 0.654 0.002 0.740 0.015
PTK2B 0.775 0.019 0.831 0.028 0.810 0.017
PTPN1 0.721 0.012 0.737 0.024
PYCARD 0.702 0.005
RAB27A 0.736 0.008
RAB30 0.761 0.011
RARB 0.746 0.010
RASSF1 0.805 0.043
RHOB 0.755 0.029 0.672 0.001
RLN1 0.742 0.036 0.740 0.036
RND3 0.607 <.001 0.633 <.001
RNF114 0.782 0.041 0.747 0.013
SDC2 0.714 0.002
SDHC 0.698 <.001 0.762 0.029
SERPINA3 0.752 0.030
SERPINB5 0.669 0.014
SH3RF2 0.705 0.012 0.568 <.001 0.755 0.016
SLC22A3 0.650 <.001 0.582 <.001
SMAD4 0.636 <.001 0.684 0.002 0.741 0.007 0.738 0.007
SMARCD1 0.757 0.001
SMO 0.790 0.049 0.766 0.013
SOD1 0.741 0.037 0.713 0.007
SORBS1 0.684 0.003 0.732 0.008 0.788 0.049
SPDEF 0.840 0.012
SPINT1 0.837 0.048
SRC 0.674 <.001 0.671 <.001
SRD5A2 0.553 <.001 0.588 <.001 0.618 <.001 0.701 <.001
ST5 0.747 0.012 0.761 0.010 0.780 0.016 0.832 0.041
STAT3 0.735 0.020
STAT5A 0.731 0.005 0.743 0.009 0.817 0.027
STAT5B 0.708 <.001 0.696 0.001
SUMO1 0.815 0.037
SVIL 0.689 0.003 0.739 0.008 0.761 0.011
TBP 0.792 0.037
TFF3 0.719 0.007 0.664 0.001
TGFB1I1 0.676 0.003 0.707 0.007 0.709 0.005 0.777 0.035
TGFB2 0.741 0.010 0.785 0.017
TGFBR2 0.759 0.022
TIMP3 0.785 0.037
TMPRSS2 0.780 0.012 0.742 <.001
TNF 0.654 0.007 0.682 0.006
TNFRSF10B 0.623 <.001 0.681 <.001 0.801 0.018 0.815 0.019
TNFSF10 0.721 0.004
TP53 0.759 0.011
TP63 0.737 0.020 0.754 0.007
TPM2 0.609 <.001 0.671 <.001 0.673 <.001 0.789 0.031
TRAF3IP2 0.795 0.041 0.727 0.005
TRO 0.793 0.033 0.768 0.027 0.814 0.023
TUBB2A 0.626 <.001 0.590 <.001
VCL 0.613 <.001 0.701 0.011
VIM 0.716 0.005 0.792 0.025
WFDC1 0.824 0.029
YY1 0.668 <.001 0.787 0.014 0.716 0.001 0.819 0.011
ZFHX3 0.732 <.001 0.709 <.001
ZFP36 0.656 0.001 0.609 <.001 0.818 0.045
ZNF827 0.750 0.022
Tables 6A and 6B provide genes that were significantly associated (p<0.05), positively or negatively, with recurrence (cRFI, bRFI) after adjusting for Gleason pattern in the primary and/or highest Gleason pattern. Increased expression of genes in Table 6A is negatively associated with good prognosis, while increased expression of gene in Table 6B is positively associated with good prognosis.
TABLE 6A
Genes significantly (p < 0.05) associated with cRFI or bRFI after
adjustment for Gleason pattern in the primary Gleason pattern or
highest Gleason pattern with a hazard ratio (HR) > 1.0 (increased
expression is negatively associated with good prognosis)
cRFI cRFI bRFI
Primary Highest Primary bRFI
Table 6A Pattern Pattern Pattern Highest
Official p- p- p- Pattern
Symbol HR value HR value HR value HR p-value
AKR1C3 1.258 0.039
ANLN 1.292 0.023 1.449 <.001 1.420 0.001
AQP2 1.178 0.008 1.287 <.001
ASAP2 1.396 0.015
ASPN 1.809 <.001 1.508 0.009 1.506 0.002 1.438 0.002
BAG5 1.367 0.012
BAX 1.234 0.044
BGN 1.465 0.009 1.342 0.046
BIRC5 1.338 0.008 1.364 0.004 1.279 0.006
BMP6 1.369 0.015 1.518 0.002
BUB1 1.239 0.024 1.227 0.001 1.236 0.004
CACNA1D 1.337 0.025
CADPS 1.280 0.029
CCNE2 1.256 0.043 1.577 <.001 1.324 0.001
CD276 1.320 0.029 1.396 0.007 1.279 0.033
CDC20 1.298 0.016 1.334 0.002 1.257 0.032 1.279 0.003
CDH7 1.258 0.047 1.338 0.013
CDKN2B 1.342 0.032 1.488 0.009
CDKN2C 1.344 0.010 1.450 <.001
CDKN3 1.284 0.012
CENPF 1.289 0.048 1.498 0.001 1.344 0.010
COL1A1 1.481 0.003 1.506 0.002
COL3A1 1.459 0.004 1.430 0.013
COL4A1 1.396 0.015
COL8A1 1.413 0.008
CRISP3 1.346 0.012 1.310 0.025
CTHRC1 1.588 0.002
DDIT4 1.363 0.020 1.379 0.028
DICER1 1.294 0.008
ENY2 1.269 0.024
FADD 1.307 0.010
FAS 1.243 0.025
FGF5 1.328 0.002
GNPTAB 1.246 0.037
GREM1 1.332 0.024 1.377 0.013 1.373 0.011
HDAC1 1.301 0.018 1.237 0.021
HSD17B4 1.277 0.011
IFN-γ 1.219 0.048
IMMT 1.230 0.049
INHBA 1.866 <.001 1.944 <.001
JAG1 1.298 0.030
KCNN2 1.378 0.020 1.282 0.017
KHDRBS3 1.353 0.029 1.305 0.014
LAMA3 1.344 <.001 1.232 0.048
LAMC1 1.396 0.015
LIMS1 1.337 0.004
LOX 1.355 0.001 1.341 0.002
LTBP2 1.304 0.045
MAGEA4 1.215 0.024
MANF 1.460 <.001
MCM6 1.287 0.042 1.214 0.046
MELK 1.329 0.002
MMP11 1.281 0.050
MRPL13 1.266 0.021
MYBL2 1.453 <.001 1.274 0.019
MYC 1.265 0.037
MYO6 1.278 0.047
NETO2 1.322 0.022
NFKB1 1.255 0.032
NOX4 1.266 0.041
OR51E1 1.566 <.001 1.428 0.003
PATE1 1.242 <.001 1.347 <.001 1.177 0.011
PCNA 1.251 0.025
PEX10 1.302 0.028
PGD 1.335 0.045 1.379 0.014 1.274 0.025
PIM1 1.254 0.019
PLA2G7 1.289 0.025 1.250 0.031
PLAU 1.267 0.031
PSMD13 1.333 0.005
PTK6 1.432 <.001 1.577 <.001 1.223 0.040
PTTG1 1.279 0.013 1.308 0.006
RAGE 1.329 0.011
RALA 1.363 0.044 1.471 0.003
RGS7 1.120 0.040 1.173 0.031
RRM1 1.490 0.004 1.527 <.001
SESN3 1.353 0.017
SFRP4 1.370 0.025
SHMT2 1.460 0.008 1.410 0.006 1.407 0.008 1.345 <.001
SKIL 1.307 0.025
SLC25A21 1.414 0.002 1.330 0.004
SMARCC2 1.219 0.049
SPARC 1.431 0.005
TFDP1 1.283 0.046 1.345 0.003
THBS2 1.456 0.005 1.431 0.012
TK1 1.214 0.015 1.222 0.006
TOP2A 1.367 0.018 1.518 0.001 1.480 <.001
TPX2 1.513 0.001 1.607 <.001 1.588 <.001 1.481 <.001
UBE2T 1.409 0.002 1.285 0.018
UGT2B15 1.216 0.009 1.182 0.021
XIAP 1.336 0.037 1.194 0.043
TABLE 6B
Genes significantly (p < 0.05) associated with cRFI or bRFI after
adjustment for Gleason pattern in the primary Gleason pattern or
highest Gleason pattern with hazard ration (HR) < 1.0 (increased
expression is positively associated with good prognosis)
cRFI cRFI bRFI
Primary Highest Primary bRFI
Table 6B Pattern Pattern Pattern Highest
Official p- p- p- Pattern
Symbol HR value HR value HR value HR p-value
AAMP 0.660 0.001 0.675 <.001 0.836 0.045
ABCA5 0.807 0.014 0.737 <.001 0.845 0.030
ABCC1 0.780 0.038 0.794 0.015
ABCG2 0.807 0.035
ABHD2 0.720 0.002
ADH5 0.750 0.034
AKAP1 0.721 <.001
ALDH1A2 0.735 0.009 0.592 <.001 0.756 0.007 0.781 0.021
ANGPT2 0.741 0.036
ANPEP 0.637 <.001 0.536 <.001
ANXA2 0.762 0.044
APOE 0.707 0.013
APRT 0.727 0.004 0.771 0.006
ATXN1 0.725 0.013
AURKA 0.784 0.037 0.735 0.003
AXIN2 0.744 0.004 0.630 <.001
AZGP1 0.672 <.001 0.720 <.001 0.764 0.001
BAD 0.687 <.001
BAK1 0.783 0.014
BCL2 0.777 0.033 0.772 0.036
BIK 0.768 0.040
BIN1 0.691 <.001
BTRC 0.776 0.029
C7 0.707 0.004 0.791 0.024
CADM1 0.587 <.001 0.593 <.001
CASP1 0.773 0.023 0.820 0.025
CAV1 0.753 0.014
CAV2 0.627 0.009 0.682 0.003
CCL2 0.740 0.019
CCNH 0.736 0.003
CCR1 0.755 0.022
CD1A 0.740 0.025
CD44 0.590 <.001 0.637 <.001
CD68 0.757 0.026
CD82 0.778 0.012 0.759 0.016
CDC25B 0.760 0.021
CDK3 0.762 0.024 0.774 0.007
CDKN1A 0.714 0.015
CDKN1C 0.738 0.014 0.768 0.021
COL6A1 0.690 <.001 0.805 0.048
CSF1 0.675 0.002 0.779 0.036
CSK 0.825 0.004
CTNNB1 0.884 0.045 0.888 0.027
CTSB 0.740 0.017 0.676 0.003 0.755 0.010
CTSD 0.673 0.031 0.722 0.009
CTSK 0.804 0.034
CTSL2 0.748 0.019
CXCL12 0.731 0.017
CYP3A5 0.523 <.001 0.518 <.001
CYR61 0.744 0.041
DAP 0.755 0.011
DARC 0.763 0.029
DDR2 0.813 0.041
DES 0.743 0.020
DHRS9 0.606 0.001
DHX9 0.916 0.021
DIAPH1 0.749 0.036 0.688 0.003
DLGAP1 0.758 0.042 0.676 0.002
DLL4 0.779 0.010
DNM3 0.732 0.007
DPP4 0.732 0.004 0.750 0.014
DPT 0.704 0.014
DUSP6 0.662 <.001 0.665 0.001
EBNA1BP2 0.828 0.019
EDNRA 0.782 0.048
EGF 0.712 0.023
EGR1 0.678 0.004 0.725 0.028
EGR3 0.680 0.006 0.738 0.027
EIF2C2 0.789 0.032
EIF2S3 0.759 0.012
ELK4 0.745 0.024
EPHA2 0.661 0.007
EPHA3 0.781 0.026 0.828 0.037
ERBB2 0.791 0.022 0.760 0.014 0.789 0.006
ERBB3 0.757 0.009
ERCC1 0.760 0.008
ESR1 0.742 0.014
ESR2 0.711 0.038
ETV4 0.714 0.035
FAM107A 0.619 <.001 0.710 0.011 0.781 0.019
FAM13C 0.664 <.001 0.686 <.001 0.813 0.014
FAM49B 0.670 <.001 0.793 0.014 0.815 0.044 0.843 0.047
FASLG 0.616 0.004 0.813 0.038
FGF10 0.751 0.028 0.766 0.019
FGF17 0.718 0.031 0.765 0.019
FGFR2 0.740 0.009 0.738 0.002
FKBP5 0.749 0.031
FLNC 0.826 0.029
FLT1 0.779 0.045 0.729 0.006
FLT4 0.815 0.024
FOS 0.657 0.003 0.656 0.004
FSD1 0.763 0.017
FYN 0.716 0.004 0.792 0.024
GADD45B 0.692 0.009 0.697 0.010
GDF15 0.767 0.016
GHR 0.701 0.002 0.704 0.002 0.640 <.001
GNRH1 0.778 0.039
GPM6B 0.749 0.010 0.750 0.010 0.827 0.037
GRB7 0.696 0.005
GSK3B 0.726 0.005
GSN 0.660 <.001 0.752 0.019
GSTM1 0.710 0.004 0.676 <.001
GSTM2 0.643 <.001 0.767 0.015
HK1 0.798 0.035
HLA-G 0.660 0.013
HLF 0.644 <.001 0.727 0.011
HNF1B 0.755 0.013
HPS1 0.756 0.006 0.791 0.043
HSD17B10 0.737 0.006
HSD3B2 0.674 0.003
HSP90AB1 0.763 0.015
HSPB1 0.787 0.020 0.778 0.015
HSPE1 0.794 0.039
ICAM1 0.664 0.003
IER3 0.699 0.003 0.693 0.010
IFIT1 0.621 <.001 0.733 0.027
IGF1 0.751 0.017 0.655 <.001
IGFBP2 0.599 <.001 0.605 <.001
IGFBP5 0.745 0.007 0.775 0.035
IGFBP6 0.671 0.005
IL1B 0.732 0.016 0.717 0.005
IL6 0.763 0.040
IL6R 0.764 0.022
IL6ST 0.647 <.001 0.739 0.012
IL8 0.711 0.015 0.694 0.006
ING5 0.729 0.007 0.727 0.003
ITGA4 0.755 0.009
ITGA5 0.743 0.018 0.770 0.034
ITGA6 0.816 0.044 0.772 0.006
ITGA7 0.680 0.004
ITGAD 0.590 0.009
ITGB4 0.663 <.001 0.658 <.001 0.759 0.004
JUN 0.656 0.004 0.639 0.003
KIAA0196 0.737 0.011
KIT 0.730 0.021 0.724 0.008
KLC1 0.755 0.035
KLK1 0.706 0.008
KLK2 0.740 0.016 0.723 0.001
KLK3 0.765 0.006 0.740 0.002
KRT1 0.774 0.042
KRT15 0.658 <.001 0.632 <.001 0.764 0.008
KRT18 0.703 0.004 0.672 <.001 0.779 0.015 0.811 0.032
KRT5 0.686 <.001 0.629 <.001 0.802 0.023
KRT8 0.763 0.034 0.771 0.022
L1CAM 0.748 0.041
LAG3 0.693 0.008 0.724 0.020
LAMA4 0.689 0.039
LAMB3 0.667 <.001 0.645 <.001 0.773 0.006
LGALS3 0.666 <.001 0.822 0.047
LIG3 0.723 0.008
LRP1 0.777 0.041 0.769 0.007
MDM2 0.688 <.001
MET 0.709 0.010 0.736 0.028 0.715 0.003
MGMT 0.751 0.031
MICA 0.705 0.002
MPPED2 0.690 0.001 0.657 <.001 0.708 <.001
MRC1 0.812 0.049
MSH6 0.860 0.049
MTSS1 0.686 0.001
MVP 0.798 0.034 0.761 0.033
MYBPC1 0.754 0.009 0.615 <.001
NCAPD3 0.739 0.021 0.664 0.005
NEXN 0.798 0.037
NFAT5 0.596 <.001 0.732 0.005
NFATC2 0.743 0.016 0.792 0.047
NOS3 0.730 0.012 0.757 0.032
OAZ1 0.732 0.020 0.705 0.002
OCLN 0.746 0.043 0.784 0.025
OLFML3 0.711 0.002 0.709 <.001 0.720 0.001
OMD 0.729 0.011 0.762 0.033
OSM 0.813 0.028
PAGE4 0.668 0.003 0.725 0.004 0.688 <.001 0.766 0.005
PCA3 0.736 0.001 0.691 <.001
PCDHGB7 0.769 0.019 0.789 0.022
PIK3CA 0.768 0.010
PIK3CG 0.792 0.019 0.758 0.009
PLG 0.682 0.009
PPAP2B 0.688 0.005 0.815 0.046
PPP1R12A 0.731 0.026 0.775 0.042
PRIMA1 0.697 0.004 0.757 0.032
PRKCA 0.743 0.019
PRKCB 0.756 0.036 0.767 0.029
PROM1 0.640 0.027 0.699 0.034 0.503 0.013
PTCH1 0.730 0.018
PTEN 0.779 0.015 0.789 0.007
PTGS2 0.644 <.001 0.703 0.007
PTHLH 0.655 0.012 0.706 0.038 0.634 0.001 0.665 0.003
PTK2B 0.779 0.023 0.702 0.002 0.806 0.015 0.806 0.024
PYCARD 0.659 0.001
RAB30 0.779 0.033 0.754 0.014
RARB 0.787 0.043 0.742 0.009
RASSF1 0.754 0.005
RHOA 0.796 0.041 0.819 0.048
RND3 0.721 0.011 0.743 0.028
SDC1 0.707 0.011
SDC2 0.745 0.002
SDHC 0.750 0.013
SERPINA3 0.730 0.016
SERPINB5 0.715 0.041
SH3RF2 0.698 0.025
SIPA1L1 0.796 0.014 0.820 0.004
SLC22A3 0.724 0.014 0.700 0.008
SMAD4 0.668 0.002 0.771 0.016
SMARCD1 0.726 <.001 0.700 0.001 0.812 0.028
SMO 0.785 0.027
SOD1 0.735 0.012
SORBS1 0.785 0.039
SPDEF 0.818 0.002
SPINT1 0.761 0.024 0.773 0.006
SRC 0.709 <.001 0.690 <.001
SRD5A1 0.746 0.010 0.767 0.024 0.745 0.003
SRD5A2 0.575 <.001 0.669 0.001 0.674 <.001 0.781 0.018
ST5 0.774 0.027
STAT1 0.694 0.004
STAT5A 0.719 0.004 0.765 0.006 0.834 0.049
STAT5B 0.704 0.001 0.744 0.012
SUMO1 0.777 0.014
SVIL 0.771 0.026
TBP 0.774 0.031
TFF3 0.742 0.015 0.719 0.024
TGFB1I1 0.763 0.048
TGFB2 0.729 0.011 0.758 0.002
TMPRSS2 0.810 0.034 0.692 <.001
TNF 0.727 0.022
TNFRSF10A 0.805 0.025
TNFRSF10B 0.581 <.001 0.738 0.014 0.809 0.034
TNFSF10 0.751 0.015 0.700 <.001
TP63 0.723 0.018 0.736 0.003
TPM2 0.708 0.010 0.734 0.014
TRAF3IP2 0.718 0.004
TRO 0.742 0.012
TSTA3 0.774 0.028
TUBB2A 0.659 <.001 0.650 <.001
TYMP 0.695 0.002
VCL 0.683 0.008
VIM 0.778 0.040
WDR19 0.775 0.014
XRCC5 0.793 0.042
YY1 0.751 0.025 0.810 0.008
ZFHX3 0.760 0.005 0.726 0.001
ZFP36 0.707 0.008 0.672 0.003
ZNF827 0.667 0.002 0.792 0.039
Tables 7A and 7B provide genes significantly associated (p<0.05), positively or negatively, with clinical recurrence (cRFI) in negative TMPRSS fusion specimens in the primary or highest Gleason pattern specimen. Increased expression of genes in Table 7A is negatively associated with good prognosis, while increased expression of genes in Table 7B is positively associated with good prognosis.
TABLE 7A
Genes significantly (p < 0.05) associated with cRFI for TMPRSS2-
ERG fusion negative in the primary Gleason pattern or highest
Gleason pattern with hazard ratio (HR) >1.0 (increased expression
is negatively associated with good prognosis)
Table 7A Primary Pattern Highest Pattern
Official Symbol HR p-value HR p-value
ANLN 1.42 0.012 1.36 0.004
AQP2 1.25 0.033
ASPN 2.48 <.001 1.65 <.001
BGN 2.04 <.001 1.45 0.007
BIRC5 1.59 <.001 1.37 0.005
BMP6 1.95 <.001 1.43 0.012
BMPR1B 1.93 0.002
BUB1 1.51 <.001 1.35 <.001
CCNE2 1.48 0.007
CD276 1.93 <.001 1.79 <.001
CDC20 1.49 0.004 1.47 <.001
CDC6 1.52 0.009 1.34 0.022
CDKN2B 1.54 0.008 1.55 0.003
CDKN2C 1.55 0.003 1.57 <.001
CDKN3 1.34 0.026
CENPF 1.63 0.002 1.33 0.018
CKS2 1.50 0.026 1.43 0.009
CLTC 1.46 0.014
COL1A1 1.98 <.001 1.50 0.002
COL3A1 2.03 <.001 1.42 0.007
COL4A1 1.81 0.002
COL8A1 1.63 0.004 1.60 0.001
CRISP3 1.31 0.016
CTHRC1 1.67 0.006 1.48 0.005
DDIT4 1.49 0.037
ENY2 1.29 0.039
EZH2 1.35 0.016
F2R 1.46 0.034 1.46 0.007
FAP 1.66 0.006 1.38 0.012
FGF5 1.46 0.001
GNPTAB 1.49 0.013
HSD17B4 1.34 0.039 1.44 0.002
INHBA 2.92 <.001 2.19 <.001
JAG1 1.38 0.042
KCNN2 1.71 0.002 1.73 <.001
KHDRBS3 1.46 0.015
KLK14 1.28 0.034
KPNA2 1.63 0.016
LAMC1 1.41 0.044
LOX 1.29 0.036
LTBP2 1.57 0.017
MELK 1.38 0.029
MMP11 1.69 0.002 1.42 0.004
MYBL2 1.78 <.001 1.49 <.001
NETO2 2.01 <.001 1.43 0.007
NME1 1.38 0.017
PATE1 1.43 <.001 1.24 0.005
PEX10 1.46 0.030
PGD 1.77 0.002
POSTN 1.49 0.037 1.34 0.026
PPFIA3 1.51 0.012
PPP3CA 1.46 0.033 1.34 0.020
PTK6 1.69 <.001 1.56 <.001
PTTG1 1.35 0.028
RAD51 1.32 0.048
RALBP1 1.29 0.042
RGS7 1.18 0.012 1.32 0.009
RRM1 1.57 0.016 1.32 0.041
RRM2 1.30 0.039
SAT1 1.61 0.007
SESN3 1.76 <.001 1.36 0.020
SFRP4 1.55 0.016 1.48 0.002
SHMT2 2.23 <.001 1.59 <.001
SPARC 1.54 0.014
SQLE 1.86 0.003
STMN1 2.14 <.001
THBS2 1.79 <.001 1.43 0.009
TK1 1.30 0.026
TOP2A 2.03 <.001 1.47 0.003
TPD52 1.63 0.003
TPX2 2.11 <.001 1.63 <.001
TRAP1 1.46 0.023
UBE2C 1.57 <.001 1.58 <.001
UBE2G1 1.56 0.008
UBE2T 1.75 <.001
UGT2B15 1.31 0.036 1.33 0.004
UHRF1 1.46 0.007
UTP23 1.52 0.017
TABLE 7B
Genes significantly (p < 0.05) associated with cRFI for TMPRSS2-
ERG fusion negative in the primary Gleason pattern or highest
Gleason pattern with hazard ratio (HR) <1.0 (increased expression
is positively associated with good prognosis)
Table 7B Primary Pattern Highest Pattern
Official Symbol HR p-value HR p-value
AAMP 0.56 <.001 0.65 0.001
ABCA5 0.64 <.001 0.71 <.001
ABCB1 0.62 0.004
ABCC3 0.74 0.031
ABCG2 0.78 0.050
ABHD2 0.71 0.035
ACOX2 0.54 <.001 0.71 0.007
ADH5 0.49 <.001 0.61 <.001
AKAP1 0.77 0.031 0.76 0.013
AKR1C1 0.65 0.006 0.78 0.044
AKT1 0.72 0.020
AKT3 0.75 <.001
ALDH1A2 0.53 <.001 0.60 <.001
AMPD3 0.62 <.001 0.78 0.028
ANPEP 0.54 <.001 0.61 <.001
ANXA2 0.63 0.008 0.74 0.016
ARHGAP29 0.67 0.005 0.77 0.016
ARHGDIB 0.64 0.013
ATP5J 0.57 0.050
ATXN1 0.61 0.004 0.77 0.043
AXIN2 0.51 <.001 0.62 <.001
AZGP1 0.61 <.001 0.64 <.001
BCL2 0.64 0.004 0.75 0.029
BIN1 0.52 <.001 0.74 0.010
BTG3 0.75 0.032 0.75 0.010
BTRC 0.69 0.011
C7 0.51 <.001 0.67 <.001
CADM1 0.49 <.001 0.76 0.034
CASP1 0.71 0.010 0.74 0.007
CAV1 0.73 0.015
CCL5 0.67 0.018 0.67 0.003
CCNH 0.63 <.001 0.75 0.004
CCR1 0.77 0.032
CD164 0.52 <.001 0.63 <.001
CD44 0.53 <.001 0.74 0.014
CDH10 0.69 0.040
CDH18 0.40 0.011
CDK14 0.75 0.013
CDK2 0.81 0.031
CDK3 0.73 0.022
CDKN1A 0.68 0.038
CDKN1C 0.62 0.003 0.72 0.005
COL6A1 0.54 <.001 0.70 0.004
COL6A3 0.64 0.004
CSF1 0.56 <.001 0.78 0.047
CSRP1 0.40 <.001 0.66 0.002
CTGF 0.66 0.015 0.74 0.027
CTNNB1 0.69 0.043
CTSB 0.60 0.002 0.71 0.011
CTSS 0.67 0.013
CXCL12 0.56 <.001 0.77 0.026
CYP3A5 0.43 <.001 0.63 <.001
CYR61 0.43 <.001 0.58 <.001
DAG1 0.72 0.012
DARC 0.66 0.016
DDR2 0.65 0.007
DES 0.52 <.001 0.74 0.018
DHRS9 0.54 0.007
DICER1 0.70 0.044
DLC1 0.75 0.021
DLGAP1 0.55 <.001 0.72 0.005
DNM3 0.61 0.001
DPP4 0.55 <.001 0.77 0.024
DPT 0.48 <.001 0.61 <.001
DUSP1 0.47 <.001 0.59 <.001
DUSP6 0.65 0.009 0.65 0.002
DYNLL1 0.74 0.045
EDNRA 0.61 0.002 0.75 0.038
EFNB2 0.71 0.043
EGR1 0.43 <.001 0.58 <.001
EGR3 0.47 <.001 0.66 <.001
EIF5 0.77 0.028
ELK4 0.49 <.001 0.72 0.012
EPHA2 0.70 0.007
EPHA3 0.62 <.001 0.72 0.009
EPHB2 0.68 0.009
ERBB2 0.64 <.001 0.63 <.001
ERBB3 0.69 0.018
ERCC1 0.69 0.019 0.77 0.021
ESR2 0.61 0.020
FAAH 0.57 <.001 0.77 0.035
FABP5 0.67 0.035
FAM107A 0.42 <.001 0.59 <.001
FAM13C 0.53 <.001 0.59 <.001
FAS 0.71 0.035
FASLG 0.56 0.017 0.67 0.014
FGF10 0.57 0.002
FGF17 0.70 0.039 0.70 0.010
FGF7 0.63 0.005 0.70 0.004
FGFR2 0.63 0.003 0.71 0.003
FKBP5 0.72 0.020
FLNA 0.48 <.001 0.74 0.022
FOS 0.45 <.001 0.56 <.001
FOXO1 0.59 <.001
FOXQ1 0.57 <.001 0.69 0.008
FYN 0.62 0.001 0.74 0.013
G6PD 0.77 0.014
GADD45A 0.73 0.045
GADD45B 0.45 <.001 0.64 0.001
GDF15 0.58 <.001
GHR 0.62 0.008 0.68 0.002
GPM6B 0.60 <.001 0.70 0.003
GSK3B 0.71 0.016 0.71 0.006
GSN 0.46 <.001 0.66 <.001
GSTM1 0.56 <.001 0.62 <.001
GSTM2 0.47 <.001 0.67 <.001
HGD 0.72 0.002
HIRIP3 0.69 0.021 0.69 0.002
HK1 0.68 0.005 0.73 0.005
HLA-G 0.54 0.024 0.65 0.013
HLF 0.41 <.001 0.68 0.001
HNF1B 0.55 <.001 0.59 <.001
HPS1 0.74 0.015 0.76 0.025
HSD17B3 0.65 0.031
HSPB2 0.62 0.004 0.76 0.027
ICAM1 0.61 0.010
IER3 0.55 <.001 0.67 0.003
IFIT1 0.57 <.001 0.70 0.008
IFNG 0.69 0.040
IGF1 0.63 <.001 0.59 <.001
IGF2 0.67 0.019 0.70 0.005
IGFBP2 0.53 <.001 0.63 <.001
IGFBP5 0.57 <.001 0.71 0.006
IGFBP6 0.41 <.001 0.71 0.012
IL10 0.59 0.020
IL1B 0.53 <.001 0.70 0.005
IL6 0.55 0.001
IL6ST 0.45 <.001 0.68 <.001
IL8 0.60 0.005 0.70 0.008
ILK 0.68 0.029 0.76 0.036
ING5 0.54 <.001 0.82 0.033
ITGA1 0.66 0.017
ITGA3 0.70 0.020
ITGA5 0.64 0.011
ITGA6 0.66 0.003 0.74 0.006
ITGA7 0.50 <.001 0.71 0.010
ITGB4 0.63 0.014 0.73 0.010
ITPR1 0.55 <.001
ITPR3 0.76 0.007
JUN 0.37 <.001 0.54 <.001
JUNB 0.58 0.002 0.71 0.016
KCTD12 0.68 0.017
KIT 0.49 0.002 0.76 0.043
KLC1 0.61 0.005 0.77 0.045
KLF6 0.65 0.009
KLK1 0.68 0.036
KLK10 0.76 0.037
KLK2 0.64 <.001 0.73 0.006
KLK3 0.65 <.001 0.76 0.021
KLRK1 0.63 0.005
KRT15 0.52 <.001 0.58 <.001
KRT18 0.46 <.001
KRT5 0.51 <.001 0.58 <.001
KRT8 0.53 <.001
L1CAM 0.65 0.031
LAG3 0.58 0.002 0.76 0.033
LAMA4 0.52 0.018
LAMB3 0.60 0.002 0.65 0.003
LGALS3 0.52 <.001 0.71 0.002
LIG3 0.65 0.011
LRP1 0.61 0.001 0.75 0.040
MGMT 0.66 0.003
MICA 0.59 0.001 0.68 0.001
MLXIP 0.70 0.020
MMP2 0.68 0.022
MMP9 0.67 0.036
MPPED2 0.57 <.001 0.66 <.001
MRC1 0.69 0.028
MTSS1 0.63 0.005 0.79 0.037
MVP 0.62 <.001
MYBPC1 0.53 <.001 0.70 0.011
NCAM1 0.70 0.039 0.77 0.042
NCAPD3 0.52 <.001 0.59 <.001
NDRG1 0.69 0.008
NEXN 0.62 0.002
NFAT5 0.45 <.001 0.59 <.001
NFATC2 0.68 0.035 0.75 0.036
NFKBIA 0.70 0.030
NRG1 0.59 0.022 0.71 0.018
OAZ1 0.69 0.018 0.62 <.001
OLFML3 0.59 <.001 0.72 0.003
OR51E2 0.73 0.013
PAGE4 0.42 <.001 0.62 <.001
PCA3 0.53 <.001
PCDHGB7 0.70 0.032
PGF 0.68 0.027 0.71 0.013
PGR 0.76 0.041
PIK3C2A 0.80 <.001
PIK3CA 0.61 <.001 0.80 0.036
PIK3CG 0.67 0.001 0.76 0.018
PLP2 0.65 0.015 0.72 0.010
PPAP2B 0.45 <.001 0.69 0.003
PPP1R12A 0.61 0.007 0.73 0.017
PRIMA1 0.51 <.001 0.68 0.004
PRKCA 0.55 <.001 0.74 0.009
PRKCB 0.55 <.001
PROM1 0.67 0.042
PROS1 0.73 0.036
PTCH1 0.69 0.024 0.72 0.010
PTEN 0.54 <.001 0.64 <.001
PTGS2 0.48 <.001 0.55 <.001
PTH1R 0.57 0.003 0.77 0.050
PTHLH 0.55 0.010
PTK2B 0.56 <.001 0.70 0.001
PYCARD 0.73 0.009
RAB27A 0.65 0.009 0.71 0.014
RAB30 0.59 0.003 0.72 0.010
RAGE 0.76 0.011
RARB 0.59 <.001 0.63 <.001
RASSF1 0.67 0.003
RB1 0.67 0.006
RFX1 0.71 0.040 0.70 0.003
RHOA 0.71 0.038 0.65 <.001
RHOB 0.58 0.001 0.71 0.006
RND3 0.54 <.001 0.69 0.003
RNF114 0.59 0.004 0.68 0.003
SCUBE2 0.77 0.046
SDHC 0.72 0.028 0.76 0.025
SEC23A 0.75 0.029
SEMA3A 0.61 0.004 0.72 0.011
SEPT9 0.66 0.013 0.76 0.036
SERPINB5 0.75 0.039
SH3RF2 0.44 <.001 0.48 <.001
SHH 0.74 0.049
SLC22A3 0.42 <.001 0.61 <.001
SMAD4 0.45 <.001 0.66 <.001
SMARCD1 0.69 0.016
SOD1 0.68 0.042
SORBS1 0.51 <.001 0.73 0.012
SPARCL1 0.58 <.001 0.77 0.040
SPDEF 0.77 <.001
SPINT1 0.65 0.004 0.79 0.038
SRC 0.61 <.001 0.69 0.001
SRD5A2 0.39 <.001 0.55 <.001
ST5 0.61 <.001 0.73 0.012
STAT1 0.64 0.006
STAT3 0.63 0.010
STAT5A 0.62 0.001 0.70 0.003
STAT5B 0.58 <.001 0.73 0.009
SUMO1 0.66 <.001
SVIL 0.57 0.001 0.74 0.022
TBP 0.65 0.002
TFF1 0.65 0.021
TFF3 0.58 <.001
TGFB1I1 0.51 <.001 0.75 0.026
TGFB2 0.48 <.001 0.62 <.001
TGFBR2 0.61 0.003
TIAM1 0.68 0.019
TIMP2 0.69 0.020
TIMP3 0.58 0.002
TNFRSF10A 0.73 0.047
TNFRSF10B 0.47 <.001 0.70 0.003
TNFSF10 0.56 0.001
TP63 0.67 0.001
TPM1 0.58 0.004 0.73 0.017
TPM2 0.46 <.001 0.70 0.005
TRA2A 0.68 0.013
TRAF3IP2 0.73 0.041 0.71 0.004
TRO 0.72 0.016 0.71 0.004
TUBB2A 0.53 <.001 0.73 0.021
TYMP 0.70 0.011
VCAM1 0.69 0.041
VCL 0.46 <.001
VEGFA 0.77 0.039
VEGFB 0.71 0.035
VIM 0.60 0.001
XRCC5 0.75 0.026
YY1 0.62 0.008 0.77 0.039
ZFHX3 0.53 <.001 0.58 <.001
ZFP36 0.43 <.001 0.54 <.001
ZNF827 0.55 0.001
Tables 8A and 8B provide genes that were significantly associated (p<0.05), positively or negatively, with clinical recurrence (cRFI) in positive TMPRSS fusion specimens in the primary or highest Gleason pattern specimen. Increased expression of genes in Table 8A is negatively associated with good prognosis, while increased expression of genes in Table 8B is positively associated with good prognosis.
TABLE 8A
Genes significantly (p < 0.05) associated with cRFI for TMPRSS2-
ERG fusion positive in the primary Gleason pattern or highest
Gleason pattern with hazard ratio (HR) >1.0 (increased expression
is negatively associated with good prognosis)
Table 8A Primary Pattern Highest Pattern
Official Symbol HR p-value HR p-value
ACTR2 1.78 0.017
AKR1C3 1.44 0.013
ALCAM 1.44 0.022
ANLN 1.37 0.046 1.81 <.001
APOE 1.49 0.023 1.66 0.005
AQP2 1.30 0.013
ARHGDIB 1.55 0.021
ASPN 2.13 <.001 2.43 <.001
ATP5E 1.69 0.013 1.58 0.014
BGN 1.92 <.001 2.55 <.001
BIRC5 1.48 0.006 1.89 <.001
BMP6 1.51 0.010 1.96 <.001
BRCA2 1.41 0.007
BUB1 1.36 0.007 1.52 <.001
CCNE2 1.55 0.004 1.59 <.001
CD276 1.65 <.001
CDC20 1.68 <.001 1.74 <.001
CDH11 1.50 0.017
CDH18 1.36 <.001
CDH7 1.54 0.009 1.46 0.026
CDKN2B 1.68 0.008 1.93 0.001
CDKN2C 2.01 <.001 1.77 <.001
CDKN3 1.51 0.002 1.33 0.049
CENPF 1.51 0.007 2.04 <.001
CKS2 1.43 0.034 1.56 0.007
COL1A1 2.23 <.001 3.04 <.001
COL1A2 1.79 0.001 2.22 <.001
COL3A1 1.96 <.001 2.81 <.001
COL4A1 1.52 0.020
COL5A1 1.50 0.020
COL5A2 1.64 0.017 1.55 0.010
COL8A1 1.96 <.001 2.38 <.001
CRISP3 1.68 0.002 1.67 0.002
CTHRC1 2.06 <.001
CTNND2 1.42 0.046 1.50 0.025
CTSK 1.43 0.049
CXCR4 1.82 0.001 1.64 0.007
DDIT4 1.54 0.016 1.58 0.009
DLL4 1.51 0.007
DYNLL1 1.50 0.021 1.22 0.002
F2R 2.27 <.001 2.02 <.001
FAP 2.12 <.001
FCGR3A 1.94 0.002
FGF5 1.23 0.047
FOXP3 1.52 0.006 1.48 0.018
GNPTAB 1.44 0.042
GPR68 1.51 0.011
GREM1 1.91 <.001 2.38 <.001
HDAC1 1.43 0.048
HDAC9 1.65 <.001 1.67 0.004
HRAS 1.65 0.005 1.58 0.021
IGFBP3 1.94 <.001 1.85 <.001
INHBA 2.03 <.001 2.64 <.001
JAG1 1.41 0.027 1.50 0.008
KCTD12 1.51 0.017
KHDRBS3 1.48 0.029 1.54 0.014
KPNA2 1.46 0.050
LAMA3 1.35 0.040
LAMC1 1.77 0.012
LTBP2 1.82 <.001
LUM 1.51 0.021 1.53 0.009
MELK 1.38 0.020 1.49 0.001
MKI67 1.37 0.014
MMP11 1.73 <.001 1.69 <.001
MRPL13 1.30 0.046
MYBL2 1.56 <.001 1.72 <.001
MYLK3 1.17 0.007
NOX4 1.58 0.005 1.96 <.001
NRIP3 1.30 0.040
NRP1 1.53 0.021
OLFML2B 1.54 0.024
OSM 1.43 0.018
PATE1 1.20 <.001 1.33 <.001
PCNA 1.64 0.003
PEX10 1.41 0.041 1.64 0.003
PIK3CA 1.38 0.037
PLK1 1.52 0.009 1.67 0.002
PLOD2 1.65 0.002
POSTN 1.79 <.001 2.06 <.001
PTK6 1.67 0.002 2.38 <.001
PTTG1 1.56 0.002 1.54 0.003
RAD21 1.61 0.036 1.53 0.005
RAD51 1.33 0.009
RALA 1.95 0.004 1.60 0.007
REG4 1.43 0.042
ROBO2 1.46 0.024
RRM1 1.44 0.033
RRM2 1.50 0.003 1.48 <.001
SAT1 1.42 0.009 1.43 0.012
SEC14L1 1.64 0.002
SFRP4 2.07 <.001 2.40 <.001
SHMT2 1.52 0.030 1.60 0.001
SLC44A1 1.42 0.039
SPARC 1.93 <.001 2.21 <.001
SULF1 1.63 0.006 2.04 <.001
THBS2 1.95 <.001 2.26 <.001
THY1 1.69 0.016 1.95 0.002
TK1 1.43 0.003
TOP2A 1.57 0.002 2.11 <.001
TPX2 1.84 <.001 2.27 <.001
UBE2C 1.41 0.011 1.44 0.006
UBE2T 1.63 0.001
UHRF1 1.51 0.007 1.69 <.001
WISP1 1.47 0.045
WNT5A 1.35 0.027 1.63 0.001
ZWINT 1.36 0.045
TABLE 8B
Genes significantly (p < 0.05) associated with cRFI for TMPRSS2-
ERG fusion positive in the primary Gleason pattern or highest
Gleason pattern with hazard ratio (HR) <1.0 (increased expression
is positively associated with good prognosis)
Table 8B Primary Pattern Highest Pattern
Official Symbol HR p-value HR p-value
AAMP 0.57 0.007 0.58 <.001
ABCA5 0.80 0.044
ACE 0.65 0.023 0.55 <.001
ACOX2 0.55 <.001
ADH5 0.68 0.022
AKAP1 0.81 0.043
ALDH1A2 0.72 0.036 0.43 <.001
ANPEP 0.66 0.022 0.46 <.001
APRT 0.73 0.040
AXIN2 0.60 <.001
AZGP1 0.57 <.001 0.65 <.001
BCL2 0.69 0.035
BIK 0.71 0.045
BIN1 0.71 0.004 0.71 0.009
BTRC 0.66 0.003 0.58 <.001
C7 0.64 0.006
CADM1 0.61 <.001 0.47 <.001
CCL2 0.73 0.042
CCNH 0.69 0.022
CD44 0.56 <.001 0.58 <.001
CD82 0.72 0.033
CDC25B 0.74 0.028
CDH1 0.75 0.030 0.72 0.010
CDH19 0.56 0.015
CDK3 0.78 0.045
CDKN1C 0.74 0.045 0.70 0.014
CSF1 0.72 0.037
CTSB 0.69 0.048
CTSL2 0.58 0.005
CYP3A5 0.51 <.001 0.30 <.001
DHX9 0.89 0.006 0.87 0.012
DLC1 0.64 0.023
DLGAP1 0.69 0.010 0.49 <.001
DPP4 0.64 <.001 0.56 <.001
DPT 0.63 0.003
EGR1 0.69 0.035
EGR3 0.68 0.025
EIF2S3 0.70 0.021
EIF5 0.71 0.030
ELK4 0.71 0.041 0.60 0.003
EPHA2 0.72 0.036 0.66 0.011
EPHB4 0.65 0.007
ERCC1 0.68 0.023
ESR2 0.64 0.027
FAM107A 0.64 0.003 0.61 0.003
FAM13C 0.68 0.006 0.55 <.001
FGFR2 0.73 0.033 0.59 <.001
FKBP5 0.60 0.006
FLNC 0.68 0.024 0.65 0.012
FLT1 0.71 0.027
FOS 0.62 0.006
FOXO1 0.75 0.010
GADD45B 0.68 0.020
GHR 0.62 0.006
GPM6B 0.57 <.001
GSTM1 0.68 0.015 0.58 <.001
GSTM2 0.65 0.005 0.47 <.001
HGD 0.63 0.001 0.71 0.020
HK1 0.67 0.003 0.62 0.002
HLF 0.59 <.001
HNF1B 0.66 0.004 0.61 0.001
IER3 0.70 0.026
IGF1 0.63 0.005 0.55 <.001
IGF1R 0.76 0.049
IGFBP2 0.59 0.007 0.64 0.003
IL6ST 0.65 0.005
IL8 0.61 0.005 0.66 0.019
ILK 0.64 0.015
ING5 0.73 0.033 0.70 0.009
ITGA7 0.72 0.045 0.69 0.019
ITGB4 0.63 0.002
KLC1 0.74 0.045
KLK1 0.56 0.002 0.49 <.001
KLK10 0.68 0.013
KLK11 0.66 0.003
KLK2 0.66 0.045 0.65 0.011
KLK3 0.75 0.048 0.77 0.014
KRT15 0.71 0.017 0.50 <.001
KRT5 0.73 0.031 0.54 <.001
LAMA5 0.70 0.044
LAMB3 0.70 0.005 0.58 <.001
LGALS3 0.69 0.025
LIG3 0.68 0.022
MDK 0.69 0.035
MGMT 0.59 0.017 0.60 <.001
MGST1 0.73 0.042
MICA 0.70 0.009
MPPED2 0.72 0.031 0.54 <.001
MTSS1 0.62 0.003
MYBPC1 0.50 <.001
NCAPD3 0.62 0.007 0.38 <.001
NCOR1 0.82 0.048
NFAT5 0.60 0.001 0.62 <.001
NRG1 0.66 0.040 0.61 0.029
NUP62 0.75 0.037
OMD 0.54 <.001
PAGE4 0.64 0.005
PCA3 0.66 0.012
PCDHGB7 0.68 0.018
PGR 0.60 0.012
PPAP2B 0.62 0.010
PPP1R12A 0.73 0.031 0.58 0.003
PRIMA1 0.65 0.013
PROM1 0.41 0.013
PTCH1 0.64 0.006
PTEN 0.75 0.047
PTGS2 0.67 0.011
PTK2B 0.66 0.005
PTPN1 0.71 0.026
RAGE 0.70 0.012
RARB 0.68 0.016
RGS10 0.84 0.034
RHOB 0.66 0.016
RND3 0.63 0.004
SDHC 0.73 0.044 0.69 0.016
SERPINA3 0.67 0.011 0.51 <.001
SERPINB5 0.42 <.001
SH3RF2 0.66 0.012 0.51 <.001
SLC22A3 0.59 0.003 0.48 <.001
SMAD4 0.64 0.004 0.49 <.001
SMARCC2 0.73 0.042
SMARCD1 0.73 <.001 0.76 0.035
SMO 0.64 0.006
SNAI1 0.53 0.008
SOD1 0.60 0.003
SRC 0.64 <.001 0.61 <.001
SRD5A2 0.63 0.004 0.59 <.001
STAT3 0.64 0.014
STAT5A 0.70 0.032
STAT5B 0.74 0.034 0.63 0.003
SVIL 0.71 0.028
TGFB1I1 0.68 0.036
TMPRSS2 0.72 0.015 0.67 <.001
TNFRSF10A 0.69 0.010
TNFRSF10B 0.67 0.007 0.64 0.001
TNFRSF18 0.38 0.003
TNFSF10 0.71 0.025
TP53 0.68 0.004 0.57 <.001
TP63 0.75 0.049 0.52 <.001
TPM2 0.62 0.007
TRAF3IP2 0.71 0.017 0.68 0.005
TRO 0.72 0.033
TUBB2A 0.69 0.038
VCL 0.62 <.001
VEGFA 0.71 0.037
WWOX 0.65 0.004
ZFHX3 0.77 0.011 0.73 0.012
ZFP36 0.69 0.018
ZNF827 0.68 0.013 0.49 <.001
Tables 9A and 9B provide genes significantly associated (p<0.05), positively or negatively, with TMPRSS fusion status in the primary Gleason pattern. Increased expression of genes in Table 9A are positively associated with TMPRSS fusion positivity, while increased expression of genes in Table 10A are negatively associated with TMPRSS fusion positivity.
TABLE 9A
Genes significantly (p < 0.05) associated with TMPRSS fusion status
in the primary Gleason pattern with odds ratio (OR) >1.0 (increased
expression is positively associated with TMPRSS fusion positivity
Table 9A
Official Odds Official Odds
Symbol p-value Ratio Symbol p-value Ratio
ABCC8 <.001 1.86 MAP3K5 <.001 2.06
ALDH18A1 0.005 1.49 MAP7 <.001 2.74
ALKBH3 0.043 1.30 MSH2 0.005 1.59
ALOX5 <.001 1.66 MSH3 0.006 1.45
AMPD3 <.001 3.92 MUC1 0.012 1.42
APEX1 <.001 2.00 MYO6 <.001 3.79
ARHGDIB <.001 1.87 NCOR2 0.001 1.62
ASAP2 0.019 1.48 NDRG1 <.001 6.77
ATXN1 0.013 1.41 NETO2 <.001 2.63
BMPR1B <.001 2.37 ODC1 <.001 1.98
CACNA1D <.001 9.01 OR51E1 <.001 2.24
CADPS 0.015 1.39 PDE9A <.001 2.21
CD276 0.003 2.25 PEX10 <.001 3.41
CDH1 0.016 1.37 PGK1 0.022 1.33
CDH7 <.001 2.22 PLA2G7 <.001 5.51
CDK7 0.025 1.43 PPP3CA 0.047 1.38
COL9A2 <.001 2.58 PSCA 0.013 1.43
CRISP3 <.001 2.60 PSMD13 0.004 1.51
CTNND1 0.033 1.48 PTCH1 0.022 1.38
ECE1 <.001 2.22 PTK2 0.014 1.38
EIF5 0.023 1.34 PTK6 <.001 2.29
EPHB4 0.005 1.51 PTK7 <.001 2.45
ERG <.001 14.5 PTPRK <.001 1.80
FAM171B 0.047 1.32 RAB30 0.001 1.60
FAM73A 0.008 1.45 REG4 0.018 1.58
FASN 0.004 1.50 RELA 0.001 1.62
GNPTAB <.001 1.60 RFX1 0.020 1.43
GPS1 0.006 1.45 RGS10 <.001 1.71
GRB7 0.023 1.38 SCUBE2 0.009 1.48
HDAC1 <.001 4.95 SEPT9 <.001 3.91
HGD <.001 1.64 SH3RF2 0.004 1.48
HIP1 <.001 1.90 SH3YL1 <.001 1.87
HNF1B <.001 3.55 SHH <.001 2.45
HSPA8 0.041 1.32 SIM2 <.001 1.74
IGF1R 0.001 1.73 SIPA1L1 0.021 1.35
ILF3 <.001 1.91 SLC22A3 <.001 1.63
IMMT 0.025 1.36 SLC44A1 <.001 1.65
ITPR1 <.001 2.72 SPINT1 0.017 1.39
ITPR3 <.001 5.91 TFDP1 0.005 1.75
JAG1 0.007 1.42 TMPRSS2ERGA 0.002 14E5
KCNN2 <.001 2.80 TMPRSS2ERGB <.001 1.97
KHDRBS3 <.001 2.63 TRIM14 <.001 1.65
KIAA0247 0.019 1.38 TSTA3 0.018 1.38
KLK11 <.001 1.98 UAP1 0.046 1.39
LAMC1 0.008 1.56 UBE2G1 0.001 1.66
LAMC2 <.001 3.30 UGDH <.001 2.22
LOX 0.009 1.41 XRCC5 <.001 1.66
LRP1 0.044 1.30 ZMYND8 <.001 2.19
TABLE 9B
Genes significantly (p < 0.05) associated with TMPRSS fusion status
in the primary Gleason pattern with odds ratio (OR) <1.0 (increased
expression is negatively associated with TMPRSS fusion positivity)
Table 9B
Official Symbol p-value Odds Ratio
ABCC4 0.045 0.77
ABHD2 <.001 0.38
ACTR2 0.027 0.73
ADAMTS1 0.024 0.58
ADH5 <.001 0.58
AGTR2 0.016 0.64
AKAP1 0.013 0.70
AKT2 0.015 0.71
ALCAM <.001 0.45
ALDH1A2 0.004 0.70
ANPEP <.001 0.43
ANXA2 0.010 0.71
APC 0.036 0.73
APOC1 0.002 0.56
APOE <.001 0.44
ARF1 0.041 0.77
ATM 0.036 0.74
AURKB <.001 0.62
AZGP1 <.001 0.54
BBC3 0.030 0.74
BCL2 0.012 0.70
BIN1 0.021 0.74
BTG1 0.004 0.67
BTG3 0.003 0.63
C7 0.023 0.74
CADM1 0.007 0.69
CASP1 0.011 0.70
CAV1 0.011 0.71
CCND1 0.019 0.72
CCR1 0.022 0.73
CD44 <.001 0.57
CD68 <.001 0.54
CD82 0.002 0.66
CDH5 0.007 0.66
CDKN1A <.001 0.60
CDKN2B <.001 0.54
CDKN2C 0.012 0.72
CDKN3 0.037 0.77
CHN1 0.038 0.75
CKS2 <.001 0.48
COL11A1 0.017 0.72
COL1A1 <.001 0.59
COL1A2 0.001 0.62
COL3A1 0.027 0.73
COL4A1 0.043 0.76
COL5A1 0.039 0.74
COL5A2 0.026 0.73
COL6A1 0.008 0.66
COL6A3 <.001 0.59
COL8A1 0.022 0.74
CSF1 0.011 0.70
CTNNB1 0.021 0.69
CTSB <.001 0.62
CTSD 0.036 0.68
CTSK 0.007 0.70
CTSS 0.002 0.64
CXCL12 <.001 0.48
CXCR4 0.005 0.68
CXCR7 0.046 0.76
CYR61 0.004 0.65
DAP 0.002 0.64
DARC 0.021 0.73
DDR2 0.021 0.73
DHRS9 <.001 0.52
DIAPH1 <.001 0.56
DICER1 0.029 0.75
DLC1 0.013 0.72
DLGAP1 <.001 0.60
DLL4 <.001 0.57
DPT 0.006 0.68
DUSP1 0.012 0.68
DUSP6 0.001 0.62
DVL1 0.037 0.75
EFNB2 <.001 0.32
EGR1 0.003 0.65
ELK4 <.001 0.60
ERBB2 <.001 0.61
ERBB3 0.045 0.76
ESR2 0.010 0.70
ETV1 0.042 0.74
FABP5 <.001 0.21
FAM13C 0.006 0.67
FCGR3A 0.018 0.72
FGF17 0.009 0.71
FGF6 0.011 0.70
FGF7 0.003 0.63
FN1 0.006 0.69
FOS 0.035 0.74
FOXP3 0.010 0.71
GABRG2 0.029 0.74
GADD45B 0.003 0.63
GDF15 <.001 0.54
GPM6B 0.004 0.67
GPNMB 0.001 0.62
GSN 0.009 0.69
HLA-G 0.050 0.74
HLF 0.018 0.74
HPS1 <.001 0.48
HSD17B3 0.003 0.60
HSD17B4 <.001 0.56
HSPB1 <.001 0.38
HSPB2 0.002 0.62
IFI30 0.049 0.75
IFNG 0.006 0.64
IGF1 0.016 0.73
IGF2 0.001 0.57
IGFBP2 <.001 0.51
IGFBP3 <.001 0.59
IGFBP6 <.001 0.57
IL10 <.001 0.62
IL17A 0.012 0.63
ILIA 0.011 0.59
IL2 0.001 0.63
IL6ST <.001 0.52
INSL4 0.014 0.71
ITGA1 0.009 0.69
ITGA4 0.007 0.68
JUN <.001 0.59
KIT <.001 0.64
KRT76 0.016 0.70
LAG3 0.002 0.63
LAPTM5 <.001 0.58
LGALS3 <.001 0.53
LTBP2 0.011 0.71
LUM 0.012 0.70
MAOA 0.020 0.73
MAP4K4 0.007 0.68
MGST1 <.001 0.54
MMP2 <.001 0.61
MPPED2 <.001 0.45
MRC1 0.005 0.67
MTPN 0.002 0.56
MTSS1 <.001 0.53
MVP 0.009 0.72
MYBPC1 <.001 0.51
MYLK3 0.001 0.58
NCAM1 <.001 0.59
NCAPD3 <.001 0.40
NCOR1 0.004 0.69
NFKBIA <.001 0.63
NNMT 0.006 0.66
NPBWR1 0.027 0.67
OAZ1 0.049 0.64
OLFML3 <.001 0.56
OSM <.001 0.64
PAGE1 0.012 0.52
PDGFRB 0.016 0.73
PECAM1 <.001 0.55
PGR 0.048 0.77
PIK3CA <.001 0.55
PIK3CG 0.008 0.71
PLAU 0.044 0.76
PLK1 0.006 0.68
PLOD2 0.013 0.71
PLP2 0.024 0.73
PNLIPRP2 0.009 0.70
PPAP2B <.001 0.62
PRKAR2B <.001 0.61
PRKCB 0.044 0.76
PROS1 0.005 0.67
PTEN <.001 0.47
PTGER3 0.007 0.69
PTH1R 0.011 0.70
PTK2B <.001 0.61
PTPN1 0.028 0.73
RAB27A <.001 0.21
RAD51 <.001 0.51
RAD9A 0.030 0.75
RARB <.001 0.62
RASSF1 0.038 0.76
RECK 0.009 0.62
RHOB 0.004 0.64
RHOC <.001 0.56
RLN1 <.001 0.30
RND3 0.014 0.72
S100P 0.002 0.66
SDC2 <.001 0.61
SEMA3A 0.001 0.64
SMAD4 <.001 0.64
SPARC <.001 0.59
SPARCL1 <.001 0.56
SPINK1 <.001 0.26
SRD5A1 0.039 0.76
STAT1 0.026 0.74
STS 0.006 0.64
SULF1 <.001 0.53
TFF3 <.001 0.19
TGFA 0.002 0.65
TGFB1I1 0.040 0.77
TGFB2 0.003 0.66
TGFB3 <.001 0.54
TGFBR2 <.001 0.61
THY1 <.001 0.63
TIMP2 0.004 0.66
TIMP3 <.001 0.60
TMPRSS2 <.001 0.40
TNFSF11 0.026 0.63
TPD52 0.002 0.64
TRAM1 <.001 0.45
TRPC6 0.002 0.64
TUBB2A <.001 0.49
VCL <.001 0.57
VEGFB 0.033 0.73
VEGFC <.001 0.61
VIM 0.012 0.69
WISP1 0.030 0.75
WNT5A <.001 0.50
A molecular field effect was investigated, and determined that the expression levels of histologically normal-appearing cells adjacent to the tumor exhibited a molecular signature of prostate cancer. Tables 10A and 10B provide genes significantly associated (p<0.05), positively or negatively, with cRFI or bRFI in non-tumor samples. Table 10A is negatively associated with good prognosis, while increased expression of genes in Table 10B is positively associated with good prognosis.
TABLE 10A
Genes significantly (p < 0.05) associated with cRFI or bRFI in
Non-Tumor Samples with hazard ratio (HR) >1.0 (increased
expression is negatively associated with good prognosis)
Table 10A cRFI bRFI
Official Symbol HR p-value HR p-value
ALCAM 1.278 0.036
ASPN 1.309 0.032
BAG5 1.458 0.004
BRCA2 1.385 <.001
CACNA1D 1.329 0.035
CD164 1.339 0.020
CDKN2B 1.398 0.014
COL3A1 1.300 0.035
COL4A1 1.358 0.019
CTNND2 1.370 0.001
DARC 1.451 0.003
DICER1 1.345 <.001
DPP4 1.358 0.008
EFNB2 1.323 0.007
FASN 1.327 0.035
GHR 1.332 0.048
HSPA5 1.260 0.048
INHBA 1.558 <.001
KCNN2 1.264 0.045
KRT76 1.115 <.001
LAMC1 1.390 0.014
LAMC2 1.216 0.042
LIG3 1.313 0.030
MAOA 1.405 0.013
MCM6 1.307 0.036
MKI67 1.271 0.008
NEK2 1.312 0.016
NPBWR1 1.278 0.035
ODC1 1.320 0.010
PEX10 1.361 0.014
PGK1 1.488 0.004
PLA2G7 1.337 0.025
POSTN 1.306 0.043
PTK6 1.344 0.005
REG4 1.348 0.009
RGS7 1.144 0.047
SFRP4 1.394 0.009
TARP 1.412 0.011
TFF1 1.346 0.010
TGFBR2 1.310 0.035
THY1 1.300 0.038
TMPRSS2ERGA 1.333 <.001
TPD52 1.374 0.015
TRPC6 1.272 0.046
UBE2C 1.323 0.007
UHRF1 1.325 0.021
TABLE 10B
Genes significantly (p < 0.05) associated with cRFI or bRFI in
Non-Tumor Samples with hazard ratio (HR) <1.0 (increased
expression is positively associated with good prognosis)
Table 10B cRFI bRFI
Official Symbol HR p-value HR p-value
ABCA5 0.807 0.028
ABCC3 0.760 0.019 0.750 0.003
ABHD2 0.781 0.028
ADAM15 0.718 0.005
AKAP1 0.740 0.009
AMPD3 0.793 0.013
ANGPT2 0.752 0.027
ANXA2 0.776 0.035
APC 0.755 0.014
APRT 0.762 0.025
AR 0.752 0.015
ARHGDIB 0.753 <.001
BIN1 0.738 0.016
CADM1 0.711 0.004
CCNH 0.820 0.041
CCR1 0.749 0.007
CDK14 0.772 0.014
CDK3 0.819 0.044
CDKN1C 0.808 0.038
CHAF1A 0.634 0.002 0.779 0.045
CHN1 0.803 0.034
CHRAC1 0.751 0.014 0.779 0.021
COL5A1 0.736 0.012
COL5A2 0.762 0.013
COL6A1 0.757 0.032
COL6A3 0.757 0.019
CSK 0.663 <.001 0.698 <.001
CTSK 0.782 0.029
CXCL12 0.771 0.037
CXCR7 0.753 0.008
CYP3A5 0.790 0.035
DDIT4 0.725 0.017
DIAPH1 0.771 0.015
DLC1 0.744 0.004 0.807 0.015
DLGAP1 0.708 0.004
DUSP1 0.740 0.034
EDN1 0.742 0.010
EGR1 0.731 0.028
EIF3H 0.761 0.024
EIF4E 0.786 0.041
ERBB2 0.664 0.001
ERBB4 0.764 0.036
ERCC1 0.804 0.041
ESR2 0.757 0.025
EZH2 0.798 0.048
FAAH 0.798 0.042
FAM13C 0.764 0.012
FAM171B 0.755 0.005
FAM49B 0.811 0.043
FAM73A 0.778 0.015
FASLG 0.757 0.041
FGFR2 0.735 0.016
FOS 0.690 0.008
FYN 0.788 0.035 0.777 0.011
GPNMB 0.762 0.011
GSK3B 0.792 0.038
HGD 0.774 0.017
HIRIP3 0.802 0.033
HSP90AB1 0.753 0.013
HSPB1 0.764 0.021
HSPE1 0.668 0.001
IFI30 0.732 0.002
IGF2 0.747 0.006
IGFBP5 0.691 0.006
IL6ST 0.748 0.010
IL8 0.785 0.028
IMMT 0.708 <.001
ITGA6 0.747 0.008
ITGAV 0.792 0.016
ITGB3 0.814 0.034
ITPR3 0.769 0.009
JUN 0.655 0.005
KHDRBS3 0.764 0.012
KLF6 0.714 <.001
KLK2 0.813 0.048
LAMA4 0.702 0.009
LAMA5 0.744 0.011
LAPTM5 0.740 0.009
LGALS3 0.773 0.036 0.788 0.024
LIMS1 0.807 0.012
MAP3K5 0.815 0.034
MAP3K7 0.809 0.032
MAP4K4 0.735 0.018 0.761 0.010
MAPKAPK3 0.754 0.014
MICA 0.785 0.019
MTA1 0.808 0.043
MVP 0.691 0.001
MYLK3 0.730 0.039
MYO6 0.780 0.037
NCOA1 0.787 0.040
NCOR1 0.876 0.020
NDRG1 0.761 <.001
NFAT5 0.770 0.032
NFKBIA 0.799 0.018
NME2 0.753 0.005
NUP62 0.842 0.032
OAZ1 0.803 0.043
OLFML2B 0.745 0.023
OLFML3 0.743 0.009
OSM 0.726 0.018
PCA3 0.714 0.019
PECAM1 0.774 0.023
PIK3C2A 0.768 0.001
PIM1 0.725 0.011
PLOD2 0.713 0.008
PPP3CA 0.768 0.040
PROM1 0.482 <.001
PTEN 0.807 0.012
PTGS2 0.726 0.011
PTTG1 0.729 0.006
PYCARD 0.783 0.012
RAB30 0.730 0.002
RAGE 0.792 0.012
RFX1 0.789 0.016 0.792 0.010
RGS10 0.781 0.017
RUNX1 0.747 0.007
SDHC 0.827 0.036
SEC23A 0.752 0.010
SEPT9 0.889 0.006
SERPINA3 0.738 0.013
SLC25A21 0.788 0.045
SMARCD1 0.788 0.010 0.733 0.007
SMO 0.813 0.035
SRC 0.758 0.026
SRD5A2 0.738 0.005
ST5 0.767 0.022
STAT5A 0.784 0.039
TGFB2 0.771 0.027
TGFB3 0.752 0.036
THBS2 0.751 0.015
TNFRSF10B 0.739 0.010
TPX2 0.754 0.023
TRAF3IP2 0.774 0.015
TRAM1 0.868 <.001 0.880 <.001
TRIM14 0.785 0.047
TUBB2A 0.705 0.010
TYMP 0.778 0.024
UAP1 0.721 0.013
UTP23 0.763 0.007 0.826 0.018
VCL 0.837 0.040
VEGFA 0.755 0.009
WDR19 0.724 0.005
YBX1 0.786 0.027
ZFP36 0.744 0.032
ZNF827 0.770 0.043
Table 11 provides genes that are significantly associated (p<0.05) with cRFI or bRFI after adjustment for Gleason pattern or highest Gleason pattern.
TABLE 11
Genes significantly (p < 0.05) associated with cRFI or bRFI after
adjustment for Gleason pattern in the primary Gleason pattern or
highest Gleason pattern Some HR <=1.0 and some HR > 1.0
cRFI bRFI bRFI
Highest Primary Highest
Table 11 Pattern Pattern Pattern
Official Symbol HR p-value HR p-value HR p-value
HSPA5 0.710 0.009 1.288 0.030
ODC1 0.741 0.026 1.343 0.004 1.261 0.046
Tables 12A and 12B provide genes that are significantly associated (p<0.05) with prostate cancer specific survival (PCSS) in the primary Gleason pattern. Increased expression of genes in Table 12A is negatively associated with good prognosis, while increased expression of genes in Table 12B is positively associated with good prognosis.
TABLE 12A
Genes significantly (p < 0.05) associated with prostate cancer
specific survival (PCSS) in the Primary Gleason Pattern HR >1.0
(Increased expression is negatively associated with good prognosis)
Table 12A
Official Official
Symbol HR p-value Symbol HR p-value
AKR1C3 1.476 0.016 GREM1 1.942 <.001
ANLN 1.517 0.006 IFI30 1.482 0.048
APOC1 1.285 0.016 IGFBP3 1.513 0.027
APOE 1.490 0.024 INHBA 3.060 <.001
ASPN 3.055 <.001 KIF4A 1.355 0.001
ATP5E 1.788 0.012 KLK14 1.187 0.004
AURKB 1.439 0.008 LAPTM5 1.613 0.006
BGN 2.640 <.001 LTBP2 2.018 <.001
BIRC5 1.611 <.001 MMP11 1.869 <.001
BMP6 1.490 0.021 MYBL2 1.737 0.013
BRCA1 1.418 0.036 NEK2 1.445 0.028
CCNB1 1.497 0.021 NOX4 2.049 <.001
CD276 1.668 0.005 OLFML2B 1.497 0.023
CDC20 1.730 <.001 PLK1 1.603 0.006
CDH11 1.565 0.017 POSTN 2.585 <.001
CDH7 1.553 0.007 PPFIA3 1.502 0.012
CDKN2B 1.751 0.003 PTK6 1.527 0.009
CDKN2C 1.993 0.013 PTTG1 1.382 0.029
CDKN3 1.404 0.008 RAD51 1.304 0.031
CENPF 2.031 <.001 RGS7 1.251 <.001
CHAF1A 1.376 0.011 RRM2 1.515 <.001
CKS2 1.499 0.031 SAT1 1.607 0.004
COL1A1 2.574 <.001 SDC1 1.710 0.007
COL1A2 1.607 0.011 SESN3 1.399 0.045
COL3A1 2.382 <.001 SFRP4 2.384 <.001
COL4A1 1.970 <.001 SHMT2 1.949 0.003
COL5A2 1.938 0.002 SPARC 2.249 <.001
COL8A1 2.245 <.001 STMN1 1.748 0.021
CTHRC1 2.085 <.001 SULF1 1.803 0.004
CXCR4 1.783 0.007 THBS2 2.576 <.001
DDIT4 1.535 0.030 THY1 1.908 0.001
DYNLL1 1.719 0.001 TK1 1.394 0.004
F2R 2.169 <.001 TOP2A 2.119 <.001
FAM171B 1.430 0.044 TPX2 2.074 0.042
FAP 1.993 0.002 UBE2C 1.598 <.001
FCGR3A 2.099 <.001 UGT2B15 1.363 0.016
FN1 1.537 0.024 UHRF1 1.642 0.001
GPR68 1.520 0.018 ZWINT 1.570 0.010
TABLE 12B
Genes significantly (p < 0.05) associated with prostate cancer
specific survival (PCSS) in the Primary Gleason Pattern HR <1.0
(Increased expression is positively associated with good prognosis)
Table 12B
Official Official
Symbol HR p-value Symbol HR p-value
AAMP 0.649 0.040 IGFBP6 0.578 0.003
ABCA5 0.777 0.015 IL2 0.528 0.010
ABCG2 0.715 0.037 IL6ST 0.574 <.001
ACOX2 0.673 0.016 IL8 0.540 0.001
ADH5 0.522 <.001 ING5 0.688 0.015
ALDH1A2 0.561 <.001 ITGA6 0.710 0.005
AMACR 0.693 0.029 ITGA7 0.676 0.033
AMPD3 0.750 0.049 JUN 0.506 0.001
ANPEP 0.531 <.001 KIT 0.628 0.047
ATXN1 0.640 0.011 KLK1 0.523 0.002
AXIN2 0.657 0.002 KLK2 0.581 <.001
AZGP1 0.617 <.001 KLK3 0.676 <.001
BDKRB1 0.553 0.032 KRT15 0.684 0.005
BIN1 0.658 <.001 KRT18 0.536 <.001
BTRC 0.716 0.011 KRT5 0.673 0.004
C7 0.531 <.001 KRT8 0.613 0.006
CADM1 0.646 0.015 LAMB3 0.740 0.027
CASP7 0.538 0.029 LGALS3 0.678 0.007
CCNH 0.674 0.001 MGST1 0.640 0.002
CD164 0.606 <.001 MPPED2 0.629 <.001
CD44 0.687 0.016 MTSS1 0.705 0.041
CDK3 0.733 0.039 MYBPC1 0.534 <.001
CHN1 0.653 0.014 NCAPD3 0.519 <.001
COL6A1 0.681 0.015 NFAT5 0.536 <.001
CSF1 0.675 0.019 NRG1 0.467 0.007
CSRP1 0.711 0.007 OLFML3 0.646 0.001
CXCL12 0.650 0.015 OMD 0.630 0.006
CYP3A5 0.507 <.001 OR51E2 0.762 0.017
CYR61 0.569 0.007 PAGE4 0.518 <.001
DLGAP1 0.654 0.004 PCA3 0.581 <.001
DNM3 0.692 0.010 PGF 0.705 0.038
DPP4 0.544 <.001 PPAP2B 0.568 <.001
DPT 0.543 <.001 PPP1R12A 0.694 0.017
DUSP1 0.660 0.050 PRIMA1 0.678 0.014
DUSP6 0.699 0.033 PRKCA 0.632 0.001
EGR1 0.490 <.001 PRKCB 0.692 0.028
EGR3 0.561 <.001 PROM1 0.393 0.017
EIF5 0.720 0.035 PTEN 0.689 0.002
ERBB3 0.739 0.042 PTGS2 0.611 0.004
FAAH 0.636 0.010 PTH1R 0.629 0.031
FAM107A 0.541 <.001 RAB27A 0.721 0.046
FAM13C 0.526 <.001 RND3 0.678 0.029
FAS 0.689 0.030 RNF114 0.714 0.035
FGF10 0.657 0.024 SDHC 0.590 <.001
FKBP5 0.699 0.040 SERPINA3 0.710 0.050
FLNC 0.742 0.036 SH3RF2 0.570 0.005
FOS 0.556 0.005 SLC22A3 0.517 <.001
FOXQ1 0.666 0.007 SMAD4 0.528 <.001
GADD45B 0.554 0.002 SMO 0.751 0.026
GDF15 0.659 0.009 SRC 0.667 0.004
GHR 0.683 0.027 SRD5A2 0.488 <.001
GPM6B 0.666 0.005 STAT5B 0.700 0.040
GSN 0.646 0.006 SVIL 0.694 0.024
GSTM1 0.672 0.006 TFF3 0.701 0.045
GSTM2 0.514 <.001 TGFB1I1 0.670 0.029
HGD 0.771 0.039 TGFB2 0.646 0.010
HIRIP3 0.730 0.013 TNFRSF10B 0.685 0.014
HK1 0.778 0.048 TNFSF10 0.532 <.001
HLF 0.581 <.001 TPM2 0.623 0.005
HNF1B 0.643 0.013 TRO 0.767 0.049
HSD17B10 0.742 0.029 TUBB2A 0.613 0.003
IER3 0.717 0.049 VEGFB 0.780 0.034
IGF1 0.612 <.001 ZFP36 0.576 0.001
ZNF827 0.644 0.014
Analysis of gene expression and upgrading/upstaging was based on univariate ordinal logistic regression models using weighted maximum likelihood estimators for each gene in the gene list (727 test genes and 5 reference genes). P-values were generated using a Wald test of the null hypothesis that the odds ratio (OR) is one. Both unadjusted p-values and the q-value (smallest FDR at which the hypothesis test in question is rejected) were reported. Un-adjusted p-values <0.05 were considered statistically significant. Since two tumor specimens were selected for each patient, this analysis was performed using the 2 specimens from each patient as follows: (1) analysis using the primary Gleason pattern specimen from each patient (Specimens A1 and B2 as described in Table 2); and (2) analysis using the highest Gleason pattern specimen from each patient (Specimens A1 and B1 as described in Table 2). 200 genes were found to be significantly associated (p<0.05) with upgrading/upstaging in the primary Gleason pattern sample (PGP) and 203 genes were found to be significantly associated (p<0.05) with upgrading/upstaging in the highest Gleason pattern sample (HGP).
Tables 13A and 13B provide genes significantly associated (p<0.05), positively or negatively, with upgrading/upstaging in the primary and/or highest Gleason pattern. Increased expression of genes in Table 13A is positively associated with higher risk of upgrading/upstaging (poor prognosis), while increased expression of genes in Table 13B is negatively associated with risk of upgrading/upstaging (good prognosis).
TABLE 13A
Genes significantly (p < 0.05) associated with upgrading/
upstaging in the Primary Gleason Pattern (PGP) and Highest
Gleason Pattern (HGP) OR >1.0 (Increased expression is
positively associated with higher risk of upgrading/upstaging
(poor prognosis))
Table 13A PGP HGP
Gene OR p-value OR p-value
ALCAM 1.52 0.0179 1.50 0.0184
ANLN 1.36 0.0451 . .
APOE 1.42 0.0278 1.50 0.0140
ASPN 1.60 0.0027 2.06 0.0001
AURKA 1.47 0.0108 . .
AURKB . . 1.52 0.0070
BAX . . 1.48 0.0095
BGN 1.58 0.0095 1.73 0.0034
BIRC5 1.38 0.0415 . .
BMP6 1.51 0.0091 1.59 0.0071
BUB1 1.38 0.0471 1.59 0.0068
CACNA1D 1.36 0.0474 1.52 0.0078
CASP7 . . 1.32 0.0450
CCNE2 1.54 0.0042 . .
CD276 . . 1.44 0.0265
CDC20 1.35 0.0445 1.39 0.0225
CDKN2B . . 1.36 0.0415
CENPF 1.43 0.0172 1.48 0.0102
CLTC 1.59 0.0031 1.57 0.0038
COL1A1 1.58 0.0045 1.75 0.0008
COL3A1 1.45 0.0143 1.47 0.0131
COL8A1 1.40 0.0292 1.43 0.0258
CRISP3 . . 1.40 0.0256
CTHRC1 . . 1.56 0.0092
DBN1 1.43 0.0323 1.45 0.0163
DIAPH1 1.51 0.0088 1.58 0.0025
DICER1 . . 1.40 0.0293
DIO2 . . 1.49 0.0097
DVL1 . . 1.53 0.0160
F2R 1.46 0.0346 1.63 0.0024
FAP 1.47 0.0136 1.74 0.0005
FCGR3A . . 1.42 0.0221
HPN . . 1.36 0.0468
HSD17B4 . . 1.47 0.0151
HSPA8 1.65 0.0060 1.58 0.0074
IL11 1.50 0.0100 1.48 0.0113
IL1B 1.41 0.0359 . .
INHBA 1.56 0.0064 1.71 0.0042
KHDRBS3 1.43 0.0219 1.59 0.0045
KIF4A . . 1.50 0.0209
KPNA2 1.40 0.0366 . .
KRT2 . . 1.37 0.0456
KRT75 . . 1.44 0.0389
MANF . . 1.39 0.0429
MELK 1.74 0.0016 . .
MKI67 1.35 0.0408 . .
MMP11 . . 1.56 0.0057
NOX4 1.49 0.0105 1.49 0.0138
PLAUR 1.44 0.0185 . .
PLK1 . . 1.41 0.0246
PTK6 . . 1.36 0.0391
RAD51 . . 1.39 0.0300
RAF1 . . 1.58 0.0036
RRM2 1.57 0.0080 . .
SESN3 1.33 0.0465 . .
SFRP4 2.33 <0.0001 2.51 0.0015
SKIL 1.44 0.0288 1.40 0.0368
SOX4 1.50 0.0087 1.59 0.0022
SPINK1 1.52 0.0058 . .
SPP1 . . 1.42 0.0224
THBS2 . . 1.36 0.0461
TK1 . . 1.38 0.0283
TOP2A 1.85 0.0001 1.66 0.0011
TPD52 1.78 0.0003 1.64 0.0041
TPX2 1.70 0.0010 . .
UBE2G1 1.38 0.0491 . .
UBE2T 1.37 0.0425 1.46 0.0162
UHRF1 . . 1.43 0.0164
VCPIP1 . . 1.37 0.0458
TABLE 13B
Genes significantly (p < 0.05) associated with upgrading/
upstaging in the Primary Gleason Pattern (PGP) and Highest
Gleason Pattern (HGP) OR <1.0 (Increased expression is
negatively associated with higher risk of upgrading/upstaging
(good prognosis))
Table 13B PGP HGP
Gene OR p-value OR p-value
ABCC3 . . 0.70 0.0216
ABCC8 0.66 0.0121 . .
ABCG2 0.67 0.0208 0.61 0.0071
ACE . . 0.73 0.0442
ACOX2 0.46 0.0000 0.49 0.0001
ADH5 0.69 0.0284 0.59 0.0047
AIG1 . . 0.60 0.0045
AKR1C1 . . 0.66 0.0095
ALDH1A2 0.36 <0.0001 0.36 <0.0001
ALKBH3 0.70 0.0281 0.61 0.0056
ANPEP . . 0.68 0.0109
ANXA2 0.73 0.0411 0.66 0.0080
APC . . 0.68 0.0223
ATXN1 . . 0.70 0.0188
AXIN2 0.60 0.0072 0.68 0.0204
AZGP1 0.66 0.0089 0.57 0.0028
BCL2 . . 0.71 0.0182
BIN1 0.55 0.0005 . .
BTRC 0.69 0.0397 0.70 0.0251
C7 0.53 0.0002 0.51 <0.0001
CADM1 0.57 0.0012 0.60 0.0032
CASP1 0.64 0.0035 0.72 0.0210
CAV1 0.64 0.0097 0.59 0.0032
CAV2 . . 0.58 0.0107
CD164 . . 0.69 0.0260
CD82 0.67 0.0157 0.69 0.0167
CDH1 0.61 0.0012 0.70 0.0210
CDK14 0.70 0.0354 . .
CDK3 . . 0.72 0.0267
CDKN1C 0.61 0.0036 0.56 0.0003
CHN1 0.71 0.0214 . .
COL6A1 0.62 0.0125 0.60 0.0050
COL6A3 0.65 0.0080 0.68 0.0181
CSRP1 0.43 0.0001 0.40 0.0002
CTSB 0.66 0.0042 0.67 0.0051
CTSD 0.64 0.0355 . .
CTSK 0.69 0.0171 . .
CTSL1 0.72 0.0402 . .
CUL1 0.61 0.0024 0.70 0.0120
CXCL12 0.69 0.0287 0.63 0.0053
CYP3A5 0.68 0.0099 0.62 0.0026
DDR2 0.68 0.0324 0.62 0.0050
DES 0.54 0.0013 0.46 0.0002
DHX9 0.67 0.0164 . .
DLGAP1 . . 0.66 0.0086
DPP4 0.69 0.0438 0.69 0.0132
DPT 0.59 0.0034 0.51 0.0005
DUSP1 . . 0.67 0.0214
EDN1 . . 0.66 0.0073
EDNRA 0.66 0.0148 0.54 0.0005
EIF2C2 . . 0.65 0.0087
ELK4 0.55 0.0003 0.58 0.0013
ENPP2 0.65 0.0128 0.59 0.0007
EPHA3 0.71 0.0397 0.73 0.0455
EPHB2 0.60 0.0014 . .
EPHB4 0.73 0.0418 . .
EPHX3 . . 0.71 0.0419
ERCC1 0.71 0.0325 . .
FAM107A 0.56 0.0008 0.55 0.0011
FAM13C 0.68 0.0276 0.55 0.0001
FAS 0.72 0.0404 . .
FBN1 0.72 0.0395 . .
FBXW7 0.69 0.0417 . .
FGF10 0.59 0.0024 0.51 0.0001
FGF7 0.51 0.0002 0.56 0.0007
FGFR2 0.54 0.0004 0.47 <0.0001
FLNA 0.58 0.0036 0.50 0.0002
FLNC 0.45 0.0001 0.40 <0.0001
FLT4 0.61 0.0045 . .
FOXO1 0.55 0.0005 0.53 0.0005
FOXP3 0.71 0.0275 0.72 0.0354
GHR 0.59 0.0074 0.53 0.0001
GNRH1 0.72 0.0386 . .
GPM6B 0.59 0.0024 0.52 0.0002
GSN 0.65 0.0107 0.65 0.0098
GSTM1 0.44 <0.0001 0.43 <0.0001
GSTM2 0.42 <0.0001 0.39 <0.0001
HLF 0.46 <0.0001 0.47 0.0001
HPS1 0.64 0.0069 0.69 0.0134
HSPA5 0.68 0.0113 . .
HSPB2 0.61 0.0061 0.55 0.0004
HSPG2 0.70 0.0359 . .
ID3 . . 0.70 0.0245
IGF1 0.45 <0.0001 0.50 0.0005
IGF2 0.67 0.0200 0.68 0.0152
IGFBP2 0.59 0.0017 0.69 0.0250
IGFBP6 0.49 <0.0001 0.64 0.0092
IL6ST 0.56 0.0009 0.60 0.0012
ILK 0.51 0.0010 0.49 0.0004
ITGA1 0.58 0.0020 0.58 0.0016
ITGA3 0.71 0.0286 0.70 0.0221
ITGA5 . . 0.69 0.0183
ITGA7 0.56 0.0035 0.42 <0.0001
ITGB1 0.63 0.0095 0.68 0.0267
ITGB3 0.62 0.0043 0.62 0.0040
ITPR1 0.62 0.0032 . .
JUN 0.73 0.0490 0.68 0.0152
KIT 0.55 0.0003 0.57 0.0005
KLC1 . . 0.70 0.0248
KLK1 . . 0.60 0.0059
KRT15 0.58 0.0009 0.45 <0.0001
KRT5 0.70 0.0262 0.59 0.0008
LAMA4 0.56 0.0359 0.68 0.0498
LAMB3 . . 0.60 0.0017
LGALS3 0.58 0.0007 0.56 0.0012
LRP1 0.69 0.0176 . .
MAP3K7 0.70 0.0233 0.73 0.0392
MCM3 0.72 0.0320 . .
MMP2 0.66 0.0045 0.60 0.0009
MMP7 0.61 0.0015 0.65 0.0032
MMP9 0.64 0.0057 0.72 0.0399
MPPED2 0.72 0.0392 0.63 0.0042
MTA1 . . 0.68 0.0095
MTSS1 0.58 0.0007 0.71 0.0442
MVP 0.57 0.0003 0.70 0.0152
MYBPC1 . . 0.70 0.0359
NCAM1 0.63 0.0104 0.64 0.0080
NCAPD3 0.67 0.0145 0.64 0.0128
NEXN 0.54 0.0004 0.55 0.0003
NFAT5 0.72 0.0320 0.70 0.0177
NUDT6 0.66 0.0102 . .
OLFML3 0.56 0.0035 0.51 0.0011
OMD 0.61 0.0011 0.73 0.0357
PAGE4 0.42 <0.0001 0.36 <0.0001
PAK6 0.72 0.0335 . .
PCDHGB7 0.70 0.0262 0.55 0.0004
PGF 0.72 0.0358 0.71 0.0270
PLP2 0.66 0.0088 0.63 0.0041
PPAP2B 0.44 <0.0001 0.50 0.0001
PPP1R12A 0.45 0.0001 0.40 <0.0001
PRIMA1 . . 0.63 0.0102
PRKAR2B 0.71 0.0226 . .
PRKCA 0.34 <0.0001 0.42 <0.0001
PRKCB 0.66 0.0120 0.49 <0.0001
PROM1 0.61 0.0030 . .
PTEN 0.59 0.0008 0.55 0.0001
PTGER3 0.67 0.0293 . .
PTH1R 0.69 0.0259 0.71 0.0327
PTK2 0.75 0.0461 . .
PTK2B 0.70 0.0244 0.74 0.0388
PYCARD 0.73 0.0339 0.67 0.0100
RAD9A 0.64 0.0124 . .
RARB 0.67 0.0088 0.65 0.0116
RGS10 0.70 0.0219 . .
RHOB . . 0.72 0.0475
RND3 . . 0.67 0.0231
SDHC 0.72 0.0443 . .
SEC23A 0.66 0.0101 0.53 0.0003
SEMA3A 0.51 0.0001 0.69 0.0222
SH3RF2 0.55 0.0002 0.54 0.0002
SLC22A3 0.48 0.0001 0.50 0.0058
SMAD4 0.49 0.0001 0.50 0.0003
SMARCC2 0.59 0.0028 0.65 0.0052
SMO 0.60 0.0048 0.52 <0.0001
SORBS1 0.56 0.0024 0.48 0.0002
SPARCL1 0.43 0.0001 0.50 0.0001
SRD5A2 0.26 <0.0001 0.31 <0.0001
ST5 0.63 0.0103 0.52 0.0006
STAT5A 0.60 0.0015 0.61 0.0037
STAT5B 0.54 0.0005 0.57 0.0008
SUMO1 0.65 0.0066 0.66 0.0320
SVIL 0.52 0.0067 0.46 0.0003
TGFB1I1 0.44 0.0001 0.43 0.0000
TGFB2 0.55 0.0007 0.58 0.0016
TGFB3 0.57 0.0010 0.53 0.0005
TIMP1 0.72 0.0224 . .
TIMP2 0.68 0.0198 0.69 0.0206
TIMP3 0.67 0.0105 0.64 0.0065
TMPRSS2 . . 0.72 0.0366
TNFRSF10A 0.71 0.0181 . .
TNFSF10 0.71 0.0284 . .
TOP2B 0.73 0.0432 . .
TP63 0.62 0.0014 0.50 <0.0001
TPM1 0.54 0.0007 0.52 0.0002
TPM2 0.41 <0.0001 0.40 <0.0001
TPP2 0.65 0.0122 . .
TRA2A 0.72 0.0318 . .
TRAF3IP2 0.62 0.0064 0.59 0.0053
TRO 0.57 0.0003 0.51 0.0001
VCL 0.52 0.0005 0.52 0.0004
VIM 0.65 0.0072 0.65 0.0045
WDR19 0.66 0.0097 . .
WFDC1 0.58 0.0023 0.60 0.0026
ZFHX3 0.69 0.0144 0.62 0.0046
ZNF827 0.62 0.0030 0.53 0.0001
Example 3 Identification of Micrornas Associated with Clinical Recurrence and Death Due to Prostate Cancer MicroRNAs function by binding to portions of messenger RNA (mRNA) and changing how frequently the mRNA is translated into protein. They can also influence the turnover of mRNA and thus how long the mRNA remains intact in the cell. Since microRNAs function primarily as an adjunct to mRNA, this study evaluated the joint prognostic value of microRNA expression and gene (mRNA) expression. Since the expression of certain microRNAs may be a surrogate for expression of genes that are not in the assessed panel, we also evaluated the prognostic value of microRNA expression by itself.
Patients and Samples
Samples from the 127 patients with clinical recurrence and 374 patients without clinical recurrence after radical prostatectomy described in Example 2 were used in this study. The final analysis set comprised 416 samples from patients in which both gene expression and microRNA expression were successfully assayed. Of these, 106 patients exhibited clinical recurrence and 310 did not have clinical recurrence. Tissue samples were taken from each prostate sample representing (1) the primary Gleason pattern in the sample, and (2) the highest Gleason pattern in the sample. In addition, a sample of histologically normal-appearing tissue adjacent to the tumor (NAT) was taken. The number of patients in the analysis set for each tissue type and the number of them who experienced clinical recurrence or death due to prostate cancer are shown in Table 14.
TABLE 14
Number of Patients and Events in Analysis Set
Clinical Deaths Due to
Patients Recurrences Prostate Cancer
Primary Gleason
Pattern Tumor Tissue 416 106 36
Highest Gleason
Pattern Tumor Tissue 405 102 36
Normal Adjacent
Tissue 364 81 29
Assay Method
Expression of 76 test microRNAs and 5 reference microRNAs were determined from RNA extracted from fixed paraffin-embedded (FPE) tissue. MicroRNA expression in all three tissue type was quantified by reverse transcriptase polymerase chain reaction (RT-PCR) using the crossing point (Cp) obtained from the Taqman® MicroRNA Assay kit (Applied Biosystems, Inc., Carlsbad, Calif.).
Statistical Analysis
Using univariate proportional hazards regression (Cox D R, Journal of the Royal Statistical Society, Series B 34:187-220, 1972), applying the sampling weights from the cohort sampling design, and using variance estimation based on the Lin and Wei method (Lin and Wei, Journal of the American Statistical Association 84:1074-1078, 1989), microRNA expression, normalized by the average expression for the 5 reference microRNAs hsa-miR-106a, hsa-miR-146b-5p, hsa-miR-191, hsa-miR-19b, and hsa-miR-92a, and reference-normalized gene expression of the 733 genes (including the reference genes) discussed above, were assessed for association with clinical recurrence and death due to prostate cancer. Standardized hazard ratios (the proportional change in the hazard associated with a change of one standard deviation in the covariate value) were calculated.
This analysis included the following classes of predictors:
1. MicroRNAs alone
2. MicroRNA-gene pairs Tier 1
3. MicroRNA-gene pairs Tier 2
4. MicroRNA-gene pairs Tier 3
5. All other microRNA-gene pairs Tier 4
The four tiers were pre-determined based on the likelihood (Tier 1 representing the highest likelihood) that the gene-microRNA pair functionally interacted or that the microRNA was related to prostate cancer based on a review of the literature and existing microarray data sets.
False discovery rates (FDR) (Benjamini and Hochberg, Journal of the Royal Statistical Society, Series B 57:289-300, 1995) were assessed using Efron's separate class methodology (Efron, Annals of Applied Statistics 2:197-223., 2008). The false discovery rate is the expected proportion of the rejected null hypotheses that are rejected incorrectly (and thus are false discoveries). Efron's methodology allows separate FDR assessment (q-values) (Storey, Journal of the Royal Statistical Society, Series B 64:479-498, 2002) within each class while utilizing the data from all the classes to improve the accuracy of the calculation. In this analysis, the q-value for a microRNA or microRNA-gene pair can be interpreted as the empirical Bayes probability that the microRNA or microRNA-gene pair identified as being associated with clinical outcome is in fact a false discovery given the data. The separate class approach was applied to a true discovery rate degree of association (TDRDA) analysis (Crager, Statistics in Medicine 29:33-45, 2010) to determine sets of microRNAs or microRNA-gene pairs that have standardized hazard ratio for clinical recurrence or prostate cancer-specific death of at least a specified amount while controlling the FDR at 10%. For each microRNA or microRNA-gene pair, a maximum lower bound (MLB) standardized hazard ratio was computed, showing the highest lower bound for which the microRNA or microRNA-gene pair was included in a TDRDA set with 10% FDR. Also calculated was an estimate of the true standardized hazard ratio corrected for regression to the mean (RM) that occurs in subsequent studies when the best predictors are selected from a long list (Crager, 2010 above). The RM-corrected estimate of the standardized hazard ratio is a reasonable estimate of what could be expected if the selected microRNA or microRNA-gene pair were studied in a separate, subsequent study.
These analyses were repeated adjusting for clinical and pathology covariates available at the time of patient biopsy: biopsy Gleason score, baseline PSA level, and clinical T-stage (T1-T2A vs. T2B or T2C) to assess whether the microRNAs or microRNA-gene pairs have predictive value independent of these clinical and pathology covariates.
Results The analysis identified 21 microRNAs assayed from primary Gleason pattern tumor tissue that were associated with clinical recurrence of prostate cancer after radical prostatectomy, allowing a false discovery rate of 10% (Table 15). Results were similar for microRNAs assessed from highest Gleason pattern tumor tissue (Table 16), suggesting that the association of microRNA expression with clinical recurrence does not change markedly depending on the location within a tumor tissue sample. No microRNA assayed from normal adjacent tissue was associated with the risk of clinical recurrence at a false discovery rate of 10%. The sequences of the microRNAs listed in Tables 15-21 are shown in Table B.
TABLE 15
MicroRNAs Associated with Clinical Recurrence of Prostate Cancer
Primary Gleason Pattern Tumor Tissue
Absolute Standardized Hazard Ratio
95% Max. Lower RM-
q-valuea Direction Uncorrected Confidence Bound Corrected
MicroRNA p-value (FDR) of Associationb Estimate Interval @10% FDR Estimatec
hsa-miR-93 <0.0001 0.0% (+) 1.79 (1.38, 2.32) 1.19 1.51
hsa-miR-106b <0.0001 0.1% (+) 1.80 (1.38, 2.34) 1.19 1.51
hsa-miR-30e-5p <0.0001 0.1% (−) 1.63 (1.30, 2.04) 1.18 1.46
hsa-miR-21 <0.0001 0.1% (+) 1.66 (1.31, 2.09) 1.18 1.46
hsa-miR-133a <0.0001 0.1% (−) 1.72 (1.33, 2.21) 1.18 1.48
hsa-miR-449a <0.0001 0.1% (+) 1.56 (1.26, 1.92) 1.17 1.42
hsa-miR-30a 0.0001 0.1% (−) 1.56 (1.25, 1.94) 1.16 1.41
hsa-miR-182 0.0001 0.2% (+) 1.74 (1.31, 2.31) 1.17 1.45
hsa-miR-27a 0.0002 0.2% (+) 1.65 (1.27, 2.14) 1.16 1.43
hsa-miR-222 0.0006 0.5% (−) 1.47 (1.18, 1.84) 1.12 1.35
hsa-miR-103 0.0036 2.1% (+) 1.77 (1.21, 2.61) 1.12 1.36
hsa-miR-1 0.0037 2.2% (−) 1.32 (1.10, 1.60) 1.07 1.26
hsa-miR-145 0.0053 2.9% (−) 1.34 (1.09, 1.65) 1.07 1.27
hsa-miR-141 0.0060 3.2% (+) 1.43 (1.11, 1.84) 1.07 1.29
hsa-miR-92a 0.0104 4.8% (+) 1.32 (1.07, 1.64) 1.05 1.25
hsa-miR-22 0.0204 7.7% (+) 1.31 (1.03, 1.64) 1.03 1.23
hsa-miR-29b 0.0212 7.9% (+) 1.36 (1.03, 1.76) 1.03 1.24
hsa-miR-210 0.0223 8.2% (+) 1.33 (1.03, 1.70) 1.00 1.23
hsa-miR-486-5p 0.0267 9.4% (−) 1.25 (1.00, 1.53) 1.00 1.20
hsa-miR-19b 0.0280 9.7% (−) 1.24 (1.00, 1.50) 1.00 1.19
hsa-miR-205 0.0289 10.0% (−) 1.25 (1.00, 1.53) 1.00 1.20
aThe q-value is the empirical Bayes probability that the microRNA's association with clinical recurrence is a false discovery, given the data.
bDirection of association indicates where higher microRNA expression is associated with higher (+) or lower (−) risk of clinical recurrence.
cRM: regression to the mean.
TABLE 16
MicroRNAs Associated with Clinical Recurrence of Prostate Cancer
Highest Gleason Pattern Tumor Tissue
Absolute Standardized Hazard Ratio
95% Max. Lower RM-
q-valuea Direction Uncorrected Confidence Bound Corrected
MicroRNA p-value (FDR) of Associationb Estimate Interval @10% FDR Estimatec
hsa-miR-93 <0.0001 0.0% (+) 1.91 (1.48, 2.47) 1.24 1.59
hsa-miR-449a <0.0001 0.0% (+) 1.75 (1.40, 2.18) 1.23 1.54
hsa-miR-205 <0.0001 0.0% (−) 1.53 (1.29, 1.81) 1.20 1.43
hsa-miR-19b <0.0001 0.0% (−) 1.37 (1.19, 1.57) 1.15 1.32
hsa-miR-106b <0.0001 0.0% (+) 1.84 (1.39, 2.42) 1.22 1.51
hsa-miR-21 <0.0001 0.0% (+) 1.68 (1.32, 2.15) 1.19 1.46
hsa-miR-30a 0.0005 0.4% (−) 1.44 (1.17, 1.76) 1.13 1.33
hsa-miR-30e-5p 0.0010 0.6% (−) 1.37 (1.14, 1.66) 1.11 1.30
hsa-miR-133a 0.0015 0.8% (−) 1.57 (1.19, 2.07) 1.13 1.36
hsa-miR-1 0.0016 0.8% (−) 1.42 (1.14, 1.77) 1.11 1.31
hsa-miR-103 0.0021 1.1% (+) 1.69 (1.21, 2.37) 1.13 1.37
hsa-miR-210 0.0024 1.2% (+) 1.43 (1.13, 1.79) 1.11 1.31
hsa-miR-182 0.0040 1.7% (+) 1.48 (1.13, 1.93) 1.11 1.31
hsa-miR-27a 0.0055 2.1% (+) 1.46 (1.12, 1.91) 1.09 1.30
hsa-miR-222 0.0093 3.2% (−) 1.38 (1.08, 1.77) 1.08 1.27
hsa-miR-331 0.0126 3.9% (+) 1.38 (1.07, 1.77) 1.07 1.26
hsa-miR-191* 0.0143 4.3% (+) 1.38 (1.06, 1.78) 1.07 1.26
hsa-miR-425 0.0151 4.5% (+) 1.40 (1.06, 1.83) 1.07 1.26
hsa-miR-31 0.0176 5.1% (−) 1.29 (1.04, 1.60) 1.05 1.22
hsa-miR-92a 0.0202 5.6% (+) 1.31 (1.03, 1.65) 1.05 1.23
hsa-miR-155 0.0302 7.6% (−) 1.32 (1.00, 1.69) 1.03 1.22
hsa-miR-22 0.0437 9.9% (+) 1.30 (1.00, 1.67) 1.00 1.21
aThe q-value is the empirical Bayes probability that the microRNA's association with death due to prostate cancer is a false discovery, given the data.
bDirection of association indicates where higher microRNA expression is associated with higher (+) or lower (−) risk of clinical recurrence.
cRM: regression to the mean.
Table 17 shows microRNAs assayed from primary Gleason pattern tissue that were identified as being associated with the risk of prostate-cancer-specific death, with a false discovery rate of 10%. Table 18 shows the corresponding analysis for microRNAs assayed from highest Gleason pattern tissue. No microRNA assayed from normal adjacent tissue was associated with the risk of prostate-cancer-specific death at a false discovery rate of 10%.
TABLE 17
MicroRNAs Associated with Death Due to Prostate Cancer
Primary Gleason Pattern Tumor Tissue
Absolute Standardized Hazard Ratio
Max.
Lower
95% Bound RM-
q-valuea Direction Uncorrected Confidence @10% Corrected
MicroRNA p-value (FDR) of Associationb Estimate Interval FDR Estimatec
hsa-miR-30e-5p 0.0001 0.6% (−) 1.88 (1.37, 2.58) 1.15 1.46
hsa-miR-30a 0.0001 0.7% (−) 1.78 (1.33, 2.40) 1.14 1.44
hsa-miR-133a 0.0005 1.2% (−) 1.85 (1.31, 2.62) 1.13 1.41
hsa-miR-222 0.0006 1.4% (−) 1.65 (1.24, 2.20) 1.12 1.38
hsa-miR-106b 0.0024 2.7% (+) 1.85 (1.24, 2.75) 1.11 1.35
hsa-miR-1 0.0028 3.0% (−) 1.43 (1.13, 1.81) 1.08 1.30
hsa-miR-21 0.0034 3.3% (+) 1.63 (1.17, 2.25) 1.09 1.33
hsa-miR-93 0.0044 3.9% (+) 1.87 (1.21, 2.87) 1.09 1.32
hsa-miR-26a 0.0072 5.3% (−) 1.47 (1.11, 1.94) 1.07 1.29
hsa-miR-152 0.0090 6.0% (−) 1.46 (1.10, 1.95) 1.06 1.28
hsa-miR-331 0.0105 6.5% (+) 1.46 (1.09, 1.96) 1.05 1.27
hsa-miR-150 0.0159 8.3% (+) 1.51 (1.07, 2.10) 1.03 1.27
hsa-miR-27b 0.0160 8.3% (+) 1.97 (1.12, 3.42) 1.05 1.25
aThe q-value is the empirical Bayes probability that the microRNA's association with death due to prostate cancer endpoint is a false discovery, given the data.
bDirection of association indicates where higher microRNA expression is associated with higher (+) or lower (−) risk of death due to prostate cancer.
cRM: regression to the mean.
TABLE 18
MicroRNAs Associated with Death Due to Prostate Cancer
Highest Gleason Pattern Tumor Tissue
Absolute Standardized Hazard Ratio
Max.
Lower
Bound
q-valuea Direction Uncorrected 95% Confidence @10% RM-Corrected
MicroRNA p-value (FDR) of Associationb Estimate Interval FDR Estimatec
hsa-miR-27b 0.0016 6.1% (+) 2.66 (1.45, 4.88) 1.07 1.32
hsa-miR-21 0.0020 6.4% (+) 1.66 (1.21, 2.30) 1.05 1.34
hsa-miR-10a 0.0024 6.7% (+) 1.78 (1.23, 2.59) 1.05 1.34
hsa-miR-93 0.0024 6.7% (+) 1.83 (1.24, 2.71) 1.05 1.34
hsa-miR-106b 0.0028 6.8% (+) 1.79 (1.22, 2.63) 1.05 1.33
hsa-miR-150 0.0035 7.1% (+) 1.61 (1.17, 2.22) 1.05 1.32
hsa-miR-1 0.0104 9.0% (−) 1.52 (1.10, 2.09) 1.00 1.28
aThe q-value is the empirical Bayes probability that the microRNA's association with clinical endpoint is a false discovery, given the data.
bDirection of association indicates where higher microRNA expression is associated with higher (+) or lower (−) risk of death due to prostate cancer.
cRM: regression to the mean.
Table 19 and Table 20 shows the microRNAs that can be identified as being associated with the risk of clinical recurrence while adjusting for the clinical and pathology covariates of biopsy Gleason score, baseline PSA level, and clinical T-stage. The distributions of these covariates are shown in FIG. 1. Fifteen (15) of the microRNAs identified in Table 15 are also present in Table 19, indicating that these microRNAs have predictive value for clinical recurrence that is independent of the Gleason score, baseline PSA, and clinical T-stage.
Two microRNAs assayed from primary Gleason pattern tumor tissue were found that had predictive value for death due to prostate cancer independent of Gleason score, baseline PSA, and clinical T-stage (Table 21).
TABLE 19
MicroRNAs Associated with Clinical Recurrence of Prostate Cancer
Adjusting for Biopsy Gleason Score, Baseline PSA Level, and Clinical T-Stage
Primary Gleason Pattern Tumor Tissue
Absolute Standardized Hazard Ratio
Max.
Lower
95% Bound RM-
q-valuea Direction Uncorrected Confidence @10% Corrected
MicroRNA p-value (FDR) of Associationb Estimate Interval FDR Estimatec
hsa-miR-30e-5p <0.0001 0.0% (−) 1.80 (1.42, 2.27) 1.23 1.53
hsa-miR-30a <0.0001 0.0% (−) 1.75 (1.40, 2.19) 1.22 1.51
hsa-miR-93 <0.0001 0.1% (+) 1.70 (1.32, 2.20) 1.19 1.44
hsa-miR-449a 0.0001 0.1% (+) 1.54 (1.25, 1.91) 1.17 1.39
hsa-miR-133a 0.0001 0.1% (−) 1.58 (1.25, 2.00) 1.17 1.39
hsa-miR-27a 0.0002 0.1% (+) 1.66 (1.28, 2.16) 1.17 1.41
hsa-miR-21 0.0003 0.2% (+) 1.58 (1.23, 2.02) 1.16 1.38
hsa-miR-182 0.0005 0.3% (+) 1.56 (1.22, 1.99) 1.15 1.37
hsa-miR-106b 0.0008 0.5% (+) 1.57 (1.21, 2.05) 1.15 1.36
hsa-miR-222 0.0028 1.1% (−) 1.39 (1.12, 1.73) 1.11 1.28
hsa-miR-103 0.0048 1.7% (+) 1.69 (1.17, 2.43) 1.13 1.32
hsa-miR-486-5p 0.0059 2.0% (−) 1.34 (1.09, 1.65) 1.09 1.25
hsa-miR-1 0.0083 2.7% (−) 1.29 (1.07, 1.57) 1.07 1.23
hsa-miR-141 0.0088 2.8% (+) 1.43 (1.09, 1.87) 1.09 1.27
hsa-miR-200c 0.0116 3.4% (+) 1.39 (1.07, 1.79) 1.07 1.25
hsa-miR-145 0.0201 5.1% (−) 1.27 (1.03, 1.55) 1.05 1.20
hsa-miR-206 0.0329 7.2% (−) 1.40 (1.00, 1.91) 1.05 1.23
hsa-miR-29b 0.0476 9.4% (+) 1.30 (1.00, 1.69) 1.00 1.20
aThe q-value is the empirical Bayes probability that the microRNA's association with clinical recurrence is a false discovery, given the data.
bDirection of association indicates where higher microRNA expression is associated with higher (+) or lower (−) risk of clinical recurrence.
cRM: regression to the mean.
TABLE 20
MicroRNAs Associated with Clinical Recurrence of Prostate Cancer
Adjusting for Biopsy Gleason Score, Baseline PSA Level, and Clinical T-Stage
Highest Gleason Pattern Tumor Tissue
Absolute Standardized Hazard Ratio
Max.
Lower
95% Bound RM-
q-valuea Direction Uncorrected Confidence @10% Corrected
MicroRNA p-value (FDR) of Associationb Estimate Interval FDR Estimatec
hsa-miR-30a <0.0001 0.0% (−) 1.62 (1.32, 1.99) 1.20 1.43
hsa-miR-30e-5p <0.0001 0.0% (−) 1.53 (1.27, 1.85) 1.19 1.39
hsa-miR-93 <0.0001 0.0% (+) 1.76 (1.37, 2.26) 1.20 1.45
hsa-miR-205 <0.0001 0.0% (−) 1.47 (1.23, 1.74) 1.18 1.36
hsa-miR-449a 0.0001 0.1% (+) 1.62 (1.27, 2.07) 1.18 1.38
hsa-miR-106b 0.0003 0.2% (+) 1.65 (1.26, 2.16) 1.17 1.36
hsa-miR-133a 0.0005 0.2% (−) 1.51 (1.20, 1.90) 1.16 1.33
hsa-miR-1 0.0007 0.3% (−) 1.38 (1.15, 1.67) 1.13 1.28
hsa-miR-210 0.0045 1.2% (+) 1.35 (1.10, 1.67) 1.11 1.25
hsa-miR-182 0.0052 1.3% (+) 1.40 (1.10, 1.77) 1.11 1.26
hsa-miR-425 0.0066 1.6% (+) 1.48 (1.12, 1.96) 1.12 1.26
hsa-miR-155 0.0073 1.8% (−) 1.36 (1.09, 1.70) 1.10 1.24
hsa-miR-21 0.0091 2.1% (+) 1.42 (1.09, 1.84) 1.10 1.25
hsa-miR-222 0.0125 2.7% (−) 1.34 (1.06, 1.69) 1.09 1.23
hsa-miR-27a 0.0132 2.8% (+) 1.40 (1.07, 1.84) 1.09 1.23
hsa-miR-191* 0.0150 3.0% (+) 1.37 (1.06, 1.76) 1.09 1.23
hsa-miR-103 0.0180 3.4% (+) 1.45 (1.06, 1.98) 1.09 1.23
hsa-miR-31 0.0252 4.3% (−) 1.27 (1.00, 1.57) 1.07 1.19
hsa-miR-19b 0.0266 4.5% (−) 1.29 (1.00, 1.63) 1.07 1.20
hsa-miR-99a 0.0310 5.0% (−) 1.26 (1.00, 1.56) 1.06 1.18
hsa-miR-92a 0.0348 5.4% (+) 1.31 (1.00, 1.69) 1.06 1.19
hsa-miR-146b-5p 0.0386 5.8% (−) 1.29 (1.00, 1.65) 1.06 1.19
hsa-miR-145 0.0787 9.7% (−) 1.23 (1.00, 1.55) 1.00 1.15
aThe q-value is the empirical Bayes probability that the microRNA's association with clinical clinical recurrence is a false discovery, given the data.
bDirection of association indicates where higher microRNA expression is associated with higher (+) or lower (−) risk of clinical recurrence.
cRM: regression to the mean.
TABLE 21
MicroRNAs Associated with Death Due to Prostate Cancer
Adjusting for Biopsy Gleason Score, Baseline PSA Level, and Clinical T-Stage
Primary Gleason Pattern Tumor Tissue
Absolute Standardized Hazard Ratio
Max.
Lower
95% Bound RM-
q-valuea Direction Uncorrected Confidence @10% Corrected
MicroRNA p-value (FDR) of Associationb Estimate Interval FDR Estimatec
hsa-miR-30e-5p 0.0001 2.9% (−) 1.97 (1.40, 2.78) 1.09 1.39
hsa-miR-30a 0.0002 3.3% (−) 1.90 (1.36, 2.65) 1.08 1.38
aThe q-value is the empirical Bayes probability that the microRNA's association with clinical recurrence is a false discovery, given the data.
bDirection of association indicates where higher microRNA expression is associated with higher (+) or lower (−) risk of clinical recurrence.
cRM: regression to the mean.
Accordingly, the normalized expression levels of hsa-miR-93; hsa-miR-106b; hsa-miR-21; hsa-miR-449a; hsa-miR-182; hsa-miR-27a; hsa-miR-103; hsa-miR-141; hsa-miR-92a; hsa-miR-22; hsa-miR-29b; hsa-miR-210; hsa-miR-331; hsa-miR-191; hsa-miR-425; and hsa-miR-200c are positively associated with an increased risk of recurrence; and hsa-miR-30e-5p; hsa-miR-133a; hsa-miR-30a; hsa-miR-222; hsa-miR-1; hsa-miR-145; hsa-miR-486-5p; hsa-miR-19b; hsa-miR-205; hsa-miR-31; hsa-miR-155; hsa-miR-206; hsa-miR-99a; and hsa-miR-146b-5p are negatively associated with an increased risk of recurrence.
Furthermore, the normalized expression levels of hsa-miR-106b; hsa-miR-21; hsa-miR-93; hsa-miR-331; hsa-miR-150; hsa-miR-27b; and hsa-miR-10a are positively associated with an increased risk of prostate cancer specific death; and the normalized expression levels of hsa-miR-30e-5p; hsa-miR-30a; hsa-miR-133a; hsa-miR-222; hsa-miR-1; hsa-miR-26a; and hsa-miR-152 are negatively associated with an increased risk of prostate cancer specific death.
Table 22 shows the number of microRNA-gene pairs that were grouped in each tier (Tiers 1-4) and the number and percentage of those that were predictive of clinical recurrence at a false discovery rate of 10%.
TABLE 22
Number of Pairs
Total Number of Predictive of Clinical
MicroRNA-Gene Recurrence at False
Tier Pairs Discovery Rate 10% (%)
Tier 1 80 46 (57.5%)
Tier 2 719 591 (82.2%)
Tier 3 3,850 2,792 (72.5%)
Tier 4 54,724 38,264 (69.9%)
TABLE A
SEQ Forward SEQ Reverse SEQ SEQ
Official Accession ID Primer ID Primer ID Probe ID
Symbol: Number: NO Sequence: NO Sequence: NO Sequence: NO Amplicon Sequence:
AAMP NM_001087 1 GTGTGGCAGG 2 CTCCATCCAC 3 CGCTTCAAAGGA 4 GTGTGGCAGGTGGACACTAAGGAGGAGGTCTGGTCCTTTGAA
TGGACACTAA TCCAGGTCTC CCAGACCTCCTC GCGGGAGACCTGGAGTGGATGGAG
ABCA5 NM_172232 5 GGTATGGATC 6 CAGCCCGCTT 7 CACATGTGGCGA 8 GGTATGGATCCCAAAGCCAAACAGCACATGTGGCGAGCAATT
CCAAAGCCA TCTGTTTTTA GCAATTCGAACT CGAACTGCATTTAAAAACAGAAAGCGGGCTG
ABCB1 NM_000927 9 AAACACCACT 10 CAAGCCTGGA 11 CAAGCCTGGAAC 12 AAACACCACTGGAGCATTGACTACCAGGCTCGCCAATGATGCT
GGAGCATTGA ACCTATAGCC CTATAGCC GCTCAAGTTAAAGGGGCTATAGGTTCCAGGCTTG
ABCC1 NM_004996 13 TCATGGTGCC 14 CGATTGTCTT 15 ACCTGATACGTC 16 TCATGGTGCCCGTCAATGCTGTGATGGCGATGAAGACCAAGA
CGTCAATG TGCTCTTCAT TTGGTCTTCATC CGTATCAGGTGGCCCACATGAAGAGCAAAGACAATCG
GTG GCCAT
ABCC3 NM_003786 17 TCATCCTGGC 18 CCGTTGAGTG 19 TCTGTCCTGGCT 20 TCATCCTGGCGATCTACTTCCTCTGGCAGAACCTAGGTCCCTC
GATCTACTTC GAATCAGCAA GGAGTCGCTTTC TGTCCTGGCTGGAGTCGCTTTCATGGTCTTGCTGATTCCACTC
CT AT AACGG
ABCC4 NM_005845 21 AGCGCCTGGA 22 AGAGCCCCTG 23 CGGAGTCCAGTG 24 AGCGCCTGGAATCTACAACTCGGAGTCCAGTGTTTTCCCACTT
ATCTACAACT GAGAGAAGAT TTTTCCCACTTA ATCATCTTCTCTCCAGGGGCTCT
ABCC8 NM_000352 25 CGTCTGTCAC 26 TGATCCGGTT 27 AGTCTCTTGGCC 28 CGTCTGTCACTGTGGAGTGGACAGGGCTGAAGGTGGCCAAGA
TGTGGAGTGG TAGCAGGC ACCTTCAGCCCT GACTGCACCGCAGCCTGCTAAACCGGATCA
ABCG2 NM_004827 29 GGTCTCAACG 30 CTTGGATCTT 31 ACGAAGATTTGC 32 GGTCTCAACGCCATCCTGGGACCCACAGGTGGAGGCAAATCT
CCATCCTG TCCTTGCAGC CTCCACCTGTGG TCGTTATTAGATGTCTTAGCTGCAAGGAAAGATCCAAG
ABHD2 NM_007011 33 GTAGTGGGTC 34 TGAGGGTTGG 35 CAGGTGGCTCCT 36 GTAGTGGGTCTGCATGGATGTTTCAGGGATCAAAGGAGCCAC
TGCATGGATG CACTCAGG TTGATCCCTGA CTGGGCGCCTGAGTGCCAACCCTCA
T
ACE NM_000789 37 CCGCTGTACG 38 CCGTGTCTGT 39 TGCCCTCAGCAA 40 CCGCTGTACGAGGATTTCACTGCCCTCAGCAATGAAGCCTACA
AGGATTTCA GAAGCCGT TGAAGCCTACAA AGCAGGACGGCTTCACAGACACGG
ACOX2 NM_003500 41 ATGGAGGTGC 42 ACTCCGGGTA 43 TGCTCTCAACTT 44 ATGGAGGTGCCCAGAACACTGCACTCCGCAGGAAAGTTGAGA
CCAGAACAC ACTGTGGATG TCCTGCGGAGTG GCATCATCCACAGTTACCCGGAGT
ACTR2 NM_005722 45 ATCCGCATTG 46 ATCCGCTAGA 47 CCCGCAGAAAGC 48 ATCCGCATTGAAGACCCACCCCGCAGAAAGCACATGGTATTCC
AAGACCCA ACTGCACCAC ACATGGTATTCC TGGGTGGTGCAGTTCTAGCGGAT
ADAM15 NM_003815 49 GGCGGGATGT 50 ATTTCTGGGC 51 TCAGCCACAATC 52 GGCGGGATGTGGTAACAGAGACCAAGACTGTGGAGTTGGTGA
GGTAACAG CTCCGAGT ACCAACTCCACA TTGTGGCTGATCACTCGGAGGCCCAGAAAT
ADAMTS1 NM_006988 53 GGACAGGTGC 54 ATCTACAACC 55 CAAGCCAAAGGC 56 GGACAGGTGCAAGCTCATCTGCCAAGCCAAAGGCATTGGCTA
AAGCTCATCT TTGGGCTGCA ATTGGCTACTTC CTTCTTCGTTTTGCAGCCCAAGGTTGTAGAT
G A TTCG
ADH5 NM_000671 57 ATGCTGTCAT 58 CTGCTTCCTT 59 TGTCTGCCCATT 60 ATGCTGTCATCATTGTCACGGTTTGTCTGCCCATTATCTTCAT
CATTGTCACG TCCCTTTCC ATCTTCATTCTG TCTGCAAGGGAAAGGGAAAGGAAGCAG
CAA
AFAP1 NM_198595 61 GATGTCCATC 62 CAACCCTGAT 63 CCTCCAGTGCTG 64 GATGTCCATCCTTGAAACAGCCTCTTCTGGGAACACAGCACTG
CTTGAAACAG GCCTGGAG TGTTCCCAGAAG GAGGTCTCCAGGCATCAGGGTTG
C
AGTR1 NM_000685 65 AGCATTGATC 66 CTACAAGCAT 67 ATTGTTCACCCA 68 AGCATTGATCGATACCTGGCTATTGTTCACCCAATGAAGTCCC
GATACCTGGC TGTGCGTCG ATGAAGTCCCGC GCCTTCGACGCACAATGCTTGTAG
AGTR2 NM_000686 69 ACTGGCATAG 70 ATTGACTGGG 71 CCACCCAGACCC 72 ACTGGCATAGGAAATGGTATCCAGAATGGAATTTTGCTACATG
GAAATGGTAT TCTCTTTGCC CATGTAGCAAAA GGGTCTGGGTGGGGGCAAAGAGACCCAGTCAAT
CC
AIG1 NM_016108 73 CGACGGTTCT 74 TGCTCCTGCT 75 AATCGAGATGAG 76 CGACGGTTCTGCCCTTTATATTAATCGAGATGAGGACATCGCA
GCCCTTTAT GGGATACTG GACATCGCACCA CCATCAGTATCCCAGCAGGAGCA
AKAP1 NM_003488 77 TGTGGTTGGA 78 GTCTACCCAC 79 CTCCACCAGGGA 80 TGTGGTTGGAGATGAAGTGGTGTTGATAAACCGGTCCCTGGTG
GATGAAGTGG TGGGCAAGG CCGGTTTATCAA GAGCGAGGCCTTGCCCAGTGGGTAGAC
AKR1C1 BC040210 81 GTGTGTGAAG 82 CTCTGCAGGC 83 CCAAATCCCAGG 84 GTGTGTGAAGCTGAATGATGGTCACTTCATGCCTGTCCTGGGA
CTGAATGATG GCATAGGT ACAGGCATGAAG TTTGGCACCTATGCGCCTGCAGAG
G
AKR1C3 NM_003739 85 GCTTTGCCTG 86 GTCCAGTCAC 87 TGCGTCACCATC 88 GCTTTGCCTGATGTCTACCAGAAGCCCTGTGTGTGGATGGTGA
ATGTCTACCA CGGCATAGAG CACACACAGGG CGCAGAGGACGTCTCTATGCCGGTGACTGGAC
GAA A
AKT1 NM_005163 89 CGCTTCTATG 90 TCCCGGTACA 91 CAGCCCTGGACT 92 CGCTTCTATGGCGCTGAGATTGTGTCAGCCCTGGACTACCTGC
GCGCTGAGAT CCACGTTCTT ACCTGCACTCGG ACTCGGAGAAGAACGTGGTGTACCGGGA
AKT2 NM_001626 93 TCCTGCCACC 94 GGCGGTAAAT 95 CAGGTCACGTCC 96 TCCTGCCACCCTTCAAACCTCAGGTCACGTCCGAGGTCGACA
CTTCAAACC TCATCATCGA GAGGTCGACACA CAAGGTACTTCGATGATGAATTTACCGCC
A
AKT3 NM_005465 97 TTGTCTCTGC 98 CCAGCATTAG 99 TCACGGTACACA 100 TTGTCTCTGCCTTGGACTATCTACATTCCGGAAAGATTGTGTA
CTTGGACTAT ATTCTCCAAC ATCTTTCCGGA CCGTGATCTCAAGTTGGAGAATCTAATGCTGG
CTACA TTGA
ALCAM NM_001627 101 GAGGAATATG 102 GTGGCGGAGA 103 CCAGTTCCTGCC 104 GAGGAATATGGAATCCAAGGGGGCCAGTTCCTGCCGTCTGCT
GAATCCAAGG TCAAGAGG GTCTGCTCTTCT CTTCTGCCTCTTGATCTCCGCCAC
G
ALDH18A1 NM_002860 105 GATGCAGCTG 106 CTCCAGCTCA 107 CCTGAAACTTGC 108 GATGCAGCTGGAACCCAAGCTGCAGCAGGAGATGCAAGTTTC
GAACCCAA GTGGGGAA ATCTCCTGCTGC AGGATGTTCCCCACTGAGCTGGAG
ALDH1A2 NM_170696 109 CACGTCTGTC 110 GACCGTGGCT 111 TCTCTGTAGGGC 112 CACGTCTGTCCCTCTCTGCTTTCTCTGTAGGGCCCAGCTCTCA
CCTCTCTGCT CAACTTTGTA CCAGCTCTCAGG GGAATACAAAGTTGAGCCACGGTC
T
ALKBH3 NM_139178 113 TCGCTTAGTC 114 TCTGAGCCCC 115 TAAACAGGGCAG 116 TCGCTTAGTCTGCACCTCAACCGTGCGGAAAGTGACTGCCCTG
TGCACCTCAA AGTTTTTCC TCACTTTCCGCA TTTACTGAGGAAAAACTGGGGCTCAGA
C
ALOX12 NM_000697 117 AGTTCCTCAA 118 AGCACTAGCC 119 CATGCTGTTGAG 120 AGTTCCTCAATGGTGCCAACCCCATGCTGTTGAGACGCTCGAC
TGGTGCCAAC TGGAGGGC ACGCTCGACCTC CTCTCTGCCCTCCAGGCTAGTGCT
ALOX5 NM_000698 121 GAGCTGCAGG 122 GAAGCCTGAG 123 CCGCATGCCGTA 124 GAGCTGCAGGACTTCGTGAACGATGTCTACGTGTACGGCATG
ACTTCGTGA GACTTGCG CACGTAGACATC CGGGGCCGCAAGTCCTCAGGCTTC
AMACR NM_203382 125 GTCTCTGGGC 126 TGGGTATAAG 127 TCCATGTGTTTG 128 GTCTCTGGGCTGTCAGCTTTCCTTTCTCCATGTGTTTGATTTC
TGTCAGCTTT ATCCAGAACT ATTTCTCCTCAG TCCTCAGGCTGGTAGCAAGTTCTGGATCTTATACCCA
TGC GC
AMPD3 NM_000480 129 TGGTTCATCC 130 CATAAATCCG 131 TACTCTCCCAAC 132 TGGTTCATCCAGCACAAGGTCTACTCTCCCAACATGCGCTGGA
AGCACAAGG GGGCACCT ATGCGCTGGATC TCATCCAGGTGCCCCGGATTTATG
ANGPT2 NM_001147 133 CCGTGAAAGC 134 TTGCAGTGGG 135 AAGCTGACACAG 136 CCGTGAAAGCTGCTCTGTAAAAGCTGACACAGCCCTCCCAAGT
TGCTCTGTAA AAGAACAGTC CCCTCCCAAGTG GAGCAGGACTGTTCTTCCCACTGCAA
ANLN NM_018685 137 TGAAAGTCCA 138 CAGAACCAAG 139 CCAAAGAACTCG 140 TGAAAGTCCAAAACCAGGAAAATTCCAAAGAACTCGTGTCCCT
AAACCAGGAA GCTATCACCA TGTCCCTCGAGC CGAGCTGAATCTGGTGATAGCCTTGGTTCTG
ANPEP NM_001150 141 CCACCTTGGA 142 TCTCAGCGTC 143 CTCCCCAACACG 144 CCACCTTGGACCAAAGTAAAGCGTGGAATCGTTACCGCCTCCC
CCAAAGTAAA ACCTGGTAGG CTGAAACCCG CAACACGCTGAAACCCGATTCCTACCGGGTGACGCTGAGA
GC A
ANXA2 NM_004039 145 CAAGACACTA 146 CGTGTCGGGC 147 CCACCACACAGG 148 CAAGACACTAAGGGCGACTACCAGAAAGCGCTGCTGTACCTG
AGGGCGACTA TTCAGTCAT TACAGCAGCGCT TGTGGTGGAGATGACTGAAGCCCGACACG
CCA
APC NM_000038 149 GGACAGCAGG 150 ACCCACTCGA 151 CATTGGCTCCCC 152 GGACAGCAGGAATGTGTTTCTCCATACAGGTCACGGGGAGCC
AATGTGTTTC TTTGTTTCTG GTGACCTGTA AATGGTTCAGAAACAAATCGAGTGGGT
APEX1 NM_001641 153 GATGAAGCCT 154 AGGTCTCCAC 155 CTTTCGGGAAGC 156 GATGAAGCCTTTCGCAAGTTCCTGAAGGGCCTGGCTTCCCGAA
TTCGCAAGTT ACAGCACAAG CAGGCCCTT AGCCCCTTGTGCTGTGTGGAGACCT
APOC1 NM_001645 157 CCAGCCTGAT 158 CACTCTGAAT 159 AGGACAGGACCT 160 CCAGCCTGATAAAGGTCCTGCGGGCAGGACAGGACCTCCCAA
AAAGGTCCTG CCTTGCTGGA CCCAACCAAGC CCAAGCCCTCCAGCAAGGATTCAGAGTG
APOE NM_000041 161 GCCTCAAGAG 162 CCTGCACCTT 163 ACTGGCGCTGCA 164 GCCTCAAGAGCTGGTTCGAGCCCCTGGTGGAAGACATGCAGC
CTGGTTCG CTCCACCA TGTCTTCCAC GCCAGTGGGCCGGGCTGGTGGAGAAGGTGCAGG
APRT NM_000485 165 GAGGTCCTGG 166 AGGTGCCAGC 167 CCTTAAGCGAGG 168 GAGGTCCTGGAGTGCGTGAGCCTGGTGGAGCTGACCTCGCTT
AGTGCGTG TTCTCCCT TCAGCTCCACCA AAGGGCAGGGAGAAGCTGGCACCT
AQP2 NM_000486 169 GTGTGGGTGC 170 CCCTTCAGCC 171 CTCCTTCCCTTC 172 GTGTGGGTGCCAGTCCTCCTCAGGAGAAGGGGAAGGGAAGG
CAGTCCTC CTCTCAAAG CCCTTCTCCTGA AGGCCACTTTGAGAGGGCTGAAGGG
AR NM_000044 173 CGACTTCACC 174 TGACACAAGT 175 ACCATGCCGCCA 176 CGACTTCACCGCACCTGATGTGTGGTACCCTGGCGGCATGGT
GCACCTGAT GGGACTGGGA GGGTACCACA GAGCAGAGTGCCCTATCCCAGTCCCACTTGTGTCA
TA
ARF1 NM_001658 177 CAGTAGAGAT 178 ACAAGCACAT 179 CTTGTCCTTGGG 180 CAGTAGAGATCCCCGCAACTCGCTTGTCCTTGGGTCACCCTGC
CCCCGCAACT GGCTATGGAA TCACCCTGCA ATTCCATAGCCATGTGCTTGT
ARHGAP29 NM_004815 181 CACGGTCTCG 182 CAGTTGCTTG 183 ATGCCAGACCCA 184 CACGGTCTCGTGGTGAAGTCAATGCCAGACCCAGACAAAGCA
TGGTGAAGT CCCAGGAC GACAAAGCATCA TCAGCTTGTCCTGGGCAAGCAACTG
ARHGDIB NM_001175 185 TGGTCCCTAG 186 TGATGGAGGA 187 TAAAACCGGGCT 188 TGGTCCCTAGAACAAGAGGCTTAAAACCGGGCTTTCACCCAAC
AACAAGAGGC TCAGAGGGAG TTCACCCAACCT CTGCTCCCTCTGATCCTCCATCA
ASAP2 NM_003887 189 CGGCCCATCA 190 CTCTGGCCAA 191 CTGGGCTCCAAC 192 CGGCCCATCAGCTTCTACCAGCTGGGCTCCAACCAGCTTCAG
GCTTCTAC AGATACAGCG CAGCTTCAGTCT TCTAACGCTGTATCTTTGGCCAGAG
ASPN NM_017680 193 TGGACTAATC 194 AAACACCCTT 195 AGTATCACCCAG 196 TGGACTAATCTGTGGGAGCAGTTTATTCCAGTATCACCCAGGG
TGTGGGAGCA CAACACAGTC GGTGCAGCCAC TGCAGCCACACCAGGACTGTGTTGAAGGGTGTTT
C
ATM NM_000051 197 TGCTTTCTAC 198 GTTGTGGATC 199 CCAGCTGTCTTC 200 TGCTTTCTACACATGTTCAGGGATTTTTCACCAGCTGTCTTCG
ACATGTTCAG GGCTCGTT GACACTTCTCGC ACACTTCTCGCAAACGAGCCGATCCACAAC
GG
ATP5E NM_006886 201 CCGCTTTCGC 202 TGGGAGTATC 203 TCCAGCCTGTCT 204 CCGCTTTCGCTACAGCATGGTGGCCTACTGGAGACAGGCTGG
TACAGCAT GGATGTAGCT CCAGTAGGCCAC ACTCAGCTACATCCGATACTCCCA
G
ATP5J NM_ 205 GTCGACCGAC 206 CTCTACTTCC 207 CTACCCGCCATC 208 GTCGACCGACTGAAACGGCGGCCCATAATGCATTGCGATGGC
001003703 TGAAACGG GGCCCTGG GCAATGCATTAT GGGTAGGCGTGTGGGGGCGGAGCCAGGGCCGGAAGTAGAG
ATXN1 NM_000332 209 GATCGACTCC 210 GAACTGTAT 211 CGGGCTATGGCT 212 GATCGACTCCAGCACCGTAGAGAGGATTGAAGACAGCCATAG
AGCACCGTAG CACGGCCACG GTCTTCAATCCT CCCGGGCGTGGCCGTGATACAGTTC
AURKA NM_003600 213 CATCTTCCAG 214 TCCGACCTTC 215 CTCTGTGGCACC 216 CATCTTCCAGGAGGACCACTCTCTGTGGCACCCTGGACTACCT
GAGGACCACT AATCATTTCA CTGGACTACCTG GCCCCCTGAAATGATTGAAGGTCGGA
AURKB NM_004217 217 AGCTGCAGAA 218 GCATCTGCCA 219 TGACGAGCAGCG 220 AGCTGCAGAAGAGCTGCACATTTGACGAGCAGCGAACAGCCA
GAGCTGCACA ACTCCTCCAT AACAGCCACG CGATCATGGAGGAGTTGGCAGATGC
T
AXIN2 NM_004655 221 GGCTATGTCT 222 ATCCGTCAGC 223 ACCAGCGCCAAC 224 GGCTATGTCTTTGCACCAGCCACCAGCGCCAACGACAGTGAG
TTGCACCAGC GCATCACT GACAGTGAGATA ATATCCAGTGATGCGCTGACGGAT
AZGP1 NM_001185 225 GAGGCCAGCT 226 CAGGAAGGGC 227 TCTGAGATCCCA 228 GAGGCCAGCTAGGAAGCAAGGGTTGGAGGCAATGTGGGATCT
AGGAAGCAA AGCTACTGG CATTGCCTCCAA CAGACCCAGTAGCTGCCCTTCCTG
BAD NM_032989 229 GGGTCAGGGG 230 CTGCTCACTC 231 TGGGCCCAGAGC 232 GGGTCAGGGGCCTCGAGATCGGGCTTGGGCCCAGAGCATGTT
CCTCGAGAT GGCTCAAACT ATGTTCCAGATC CCAGATCCCAGAGTTTGAGCCGAGTGAGCAG
C
BAG5 NM_ 233 ACTCCTGCAA 234 ACAAACAGCT 235 ACACCGGATTTA 236 ACTCCTGCAATGAACCCTGTTGACACCGGATTTAGCTCTTGTC
001015049 TGAACCCTGT CCCCACGA GCTCTTGTCGGC GGCCTTCGTGGGGAGCTGTTTGT
BAK1 NM_001188 237 CCATTCCCAC 238 GGGAACATAG 239 ACACCCCAGACG 240 CCATTCCCACCATTCTACCTGAGGCCAGGACGTCTGGGGTGT
CATTCTACCT ACCCACCAAT TCCTGGCCT GGGGATTGGTGGGTCTATGTTCCC
BAX NM_004324 241 CCGCCGTGGA 242 TTGCCGTCAG 243 TGCCACTCGGAA 244 CCGCCGTGGACACAGACTCCCCCCGAGAGGTCTTTTTCCGAG
CACAGACT AAAACATGTC AAAGACCTCTCG TGGCAGCTGACATGTTTTCTGACGGCAA
A G
BBC3 NM_014417 245 CCTGGAGGGT 246 CTAATTGGGC 247 CATCATGGGACT 248 CCTGGAGGGTCCTGTACAATCTCATCATGGGACTCCTGCCCTT
CCTGTACAAT TCCATCTCG CCTGCCCTTACC ACCCAGGGGCCACAGAGCCCCCGAGATGGAGCCCAATTAG
BCL2 NM_000633 249 CAGATGGACC 250 CCTATGATTT 251 TTCCACGCCGAA 252 CAGATGGACCTAGTACCCACTGAGATTTCCACGCCGAAGGAC
TAGTACCCAC AAGGGCATTT GGACAGCGAT AGCGATGGGAAAAATGCCCTTAAATCATAGG
TGAGA TTCC
BDKRB1 NM_000710 253 GTGGCAGAAA 254 GAAGGGCAAG 255 ACCTGGCAGCCT 256 GTGGCAGAAATCTACCTGGCCAACCTGGCAGCCTCTGATCTG
TCTACCTGGC CCCAAGAC CTGATCTGGTGT GTGTTTGTCTTGGGCTTGCCCTTC
BGN NM_001711 257 GAGCTCCGCA 258 CTTGTTGTTC 259 CAAGGGTCTCCA 260 GAGCTCCGCAAGGATGACTTCAAGGGTCTCCAGCACCTCTAC
AGGATGAC ACCAGGACGA GCACCTCTACGC GCCCTCGTCCTGGTGAACAACAAG
BIK NM_001197 261 ATTCCTATGG 262 GGCAGGAGTG 263 CCGGTTAACTGT 264 ATTCCTATGGCTCTGCAATTGTCACCGGTTAACTGTGGCCTGT
CTCTGCAATT AATGGCTCTT GGCCTGTGCCC GCCCAGGAAGAGCCATTCACTCCTGCC
GTC C
BIN1 NM_004305 265 CCTGCAAAAG 266 CGTGGTTGAC 267 CTTCGCCTCCAG 268 CCTGCAAAAGGGAACAAGAGCCCTTCGCCTCCAGATGGCTCC
GGAACAAGAG TCTGATCTCG ATGGCTCCC CCTGCCGCCACCCCCGAGATCAGAGTCAACCACG
BIRC5 NM_ 269 TTCAGGTGGA 270 CACACAGCAG 271 TCTGCCAGACGC 272 TTCAGGTGGATGAGGAGACAGAATAGAGTGATAGGAAGCGTC
001012271 TGAGGAGACA TGGCAAAAG TTCCTATCACTC TGGCAGATACTCCTTTTGCCACTGCTGTGTG
TATTC
BMP6 NM_001718 273 GTGCAGACCT 274 CTTAGTTGGC 275 TGAACCCCGAGT 276 GTGCAGACCTTGGTTCACCTTATGAACCCCGAGTATGTCCCCA
TGGTTCACCT GCACAGCAC ATGTCCCCAAAC AACCGTGCTGTGCGCCAACTAAG
BMPR1B NM_001203 277 ACCACTTTGG 278 GCGGTGTTTG 279 ATTCACATTACC 280 ACCACTTTGGCCATCCCTGCATTTGGGGCCGCTATGGTAATGT
CCATCCCT TACCCAGTG ATAGCGGCCCCA GAATGCACTGGGTACAAACACCGC
BRCA1 NM_007294 281 TCAGGGGGCT 282 CCATTCCAGT 283 CTATGGGCCCTT 284 TCAGGGGGCTAGAAATCTGTTGCTATGGGCCCTTCACCAACAT
AGAAATCTGT TGATCTGTGG CACCAACATGC GCCCACAGATCAACTGGAATGG
BRCA2 NM_000059 285 AGTTCGTGCT 286 AAGGTAAGCT 287 CATTCTTCACTG 288 AGTTCGTGCTTTGCAAGATGGTGCAGAGCTTTATGAAGCAGTG
TTGCAAGATG GGGTCTGCTG CTTCATAAAGCT AAGAATGCAGCAGACCCAGCTTACCTT
CTGCA
BTG1 NM_001731 289 GAGGTCCGAG 290 AGTTATTTTC 291 CGCTCGTCTCTT 292 GAGGTCCGAGCGATGTGACCAGGCCGCCATCGCTCGTCTCTT
CGATGTGA GAGACAGGAG CCTCTCTCCTGC CCTCTCTCCTGCCGCCTCCTGTCTCGAAAATAACT
GC
BTG3 NM_006806 293 CCATATCGCC 294 CCAGTGATTC 295 CATGGGTACCTC 296 CCATATCGCCCAATTCCAGTGACATGGGTACCTCCTCCTGGAA
CAATTCCA CGGTCACAA CTCCTGGAATGC TGCATTGTGACCGGAATCACTGG
BTRC NM_033637 297 GTTGGGACAC 298 TGAAGCAGTC 299 CAGTCGGCCCAG 300 GTTGGGACACAGTTGGTCTGCAGTCGGCCCAGGACGGTCTAC
AGTTGGTCTG AGTTGTGCTG GACGGTCTACT TCAGCACAACTGACTGCTTCA
BUB1 NM_004336 301 CCGAGGTTAA 302 AAGACATGGC 303 TGCTGGGAGCCT 304 CCGAGGTTAATCCAGCACGTATGGGGCCAAGTGTAGGCTCCC
TCCAGCACGT GCTCTCAGTT ACACTTGGCCC AGCAGGAACTGAGAGCGCCATGTCTT
A C
C7 NM_000587 305 ATGTCTGAGT 306 AGGCCTTATG 307 ATGCTCTGCCCT 308 ATGTCTGAGTGTGAGGCGGGCGCTCTGAGATGCAGAGGGCAG
GTGAGGCGG CTGGTGACAG CTGCATCTCAGA AGCATCTCTGTCACCAGCATAAGGCCT
CACNA1D NM_000720 309 AGGACCCAGC 310 CCTACATTCC 311 CAGTACACTGGC 312 AGGACCCAGCTCCATGTGCGTTCTCAGGGAATGGACGCCAGT
TCCATGTG GTGCCATTG GTCCATTCCCTG GTACTGCCAATGGCACGGAATGTAGG
CADM1 NM_014333 313 CCACCACCAT 314 GATCCACTGC 315 TCTTCACCTGCT 316 CCACCACCATCCTTACCATCATCACAGATTCCCGAGCAGGTGA
CCTTACCATC CCTGATCG CGGGAATCTGTG AGAAGGCTCGATCAGGGCAGTGGATC
CADPS NM_003716 317 CAGCAAGGAG 318 GGTCCTCTTC 319 CTCCTGGATGGC 320 CAGCAAGGAGACTGTGCTGAGCTCCTGGATGGCCAAATTTGAT
ACTGTGCTGA TCCACGGTAG CAAATTTGATGC GCCATCTACCGTGGAGAAGAGGACC
AT
CASP1 NM_001223 321 AACTGGAGCT 322 CATCTACGCT 323 TCACAGGCATGA 324 AACTGGAGCTGAGGTTGACATCACAGGCATGACAATGCTGCTA
GAGGTTGACA GTACCCCAGA CAATGCTGCTAC CAAAATCTGGGGTACAGCGTAGATG
A
CASP3 NM_032991 325 TGAGCCTGAG 326 CCTTCCTGCG 327 TCAGCCTGTTCC 328 TGAGCCTGAGCAGAGACATGACTCAGCCTGTTCCATGAAGGC
CAGAGACATG TGGTCCAT ATGAAGGCAGAG AGAGCCATGGACCACGCAGGAAGG
A C
CASP7 NM_033338 329 GCAGCGCCGA 330 AGTCTCTCTC 331 CTTTCGCTAAAG 332 GCAGCGCCGAGACTTTTAGTTTCGCTTTCGCTAAAGGGGCCCC
GACTTTTA CGTCGCTCC GGGCCCCAGAC AGACCCTTGCTGCGGAGCGACGGAGAGAGACT
CAV1 NM_001753 333 GTGGCTCAAC 334 CAATGGCCTC 335 ATTTCAGCTGAT 336 GTGGCTCAACATTGTGTTCCCATTTCAGCTGATCAGTGGGCCT
ATTGTGTTCC CATTTTACAG CAGTGGGCCTCC CCAAGGAGGGGCTGTAAAATGGAGGCCATTG
CAV2 NM_198212 337 CTTCCCTGGG 338 CTCCTGGTCA 339 CCCGTACTGTCA 340 CTTCCCTGGGACGACTTGCCAGCTCTGAGGCATGACAGTACG
ACGACTTG CCCTTCTGG TGCCTCAGAGCT GGCCCCCAGAAGGGTGACCAGGAG
CCL2 NM_002982 341 CGCTCAGCCA 342 GCACTGAGAT 343 TGCCCCAGTCAC 344 CGCTCAGCCAGATGCAATCAATGCCCCAGTCACCTGCTGTTAT
GATGCAATC CTTCCTATTG CTGCTGTTA AACTTCACCAATAGGAAGATCTCAGTGC
GTGAA
CCL5 NM_002985 345 AGGTTCTGAG 346 ATGCTGACTT 347 ACAGAGCCCTGG 348 AGGTTCTGAGCTCTGGCTTTGCCTTGGCTTTGCCAGGGCTCTG
CTCTGGCTTT CCTTCCTGGT CAAAGCCAAG TGACCAGGAAGGAAGTCAGCAT
CCNB1 NM_031966 349 TTCAGGTTGT 350 CATCTTCTTG 351 TGTCTCCATTAT 352 TTCAGGTTGTTGCAGGAGACCATGTACATGACTGTCTCCATTA
TGCAGGAGAC GGCACACAAT TGATCGGTTCAT TTGATCGGTTCATGCAGAATAATTGTGTGCCCAAGAAGATG
GCA
CCND1 NM_001758 353 GCATGTTCGT 354 CGGTGTAGAT 355 AAGGAGACCATC 356 GCATGTTCGTGGCCTCTAAGATGAAGGAGACCATCCCCCTGA
GGCCTCTAAG GCACAGCTTC CCCCTGACGGC CGGCCGAGAAGCTGTGCATCTACACCG
A TC
CCNE2 NM_057749 357 ATGCTGTGGC 358 ACCCAAATTG 359 TACCAAGCAACC 360 ATGCTGTGGCTCCTTCCTAACTGGGGCTTTCTTGACATGTAGG
TCCTTCCTAA TGATATACAA TACATGTCAAGA TTGCTTGGTAATAACCTTTTTGTATATCACAATTTGGGT
CT AAAGGTT AAGCCC
CCNH NM_001239 361 GAGATCTTCG 362 CTGCAGACGA 363 CATCAGCGTCCT 364 GAGATCTTCGGTGGGGGTACGGGTGTTTTACGCCAGGACGCT
GTGGGGGTA GAACCCAAAC GGCGTAAAACAC GATGCGTTTGGGTTCTCGTCTGCAG
CCR1 NM_001295 365 TCCAAGACCC 366 TCGTAGGCTT 367 ACTCACCACACC 368 TCCAAGACCCAATGGGAATTCACTCACCACACCTGCAGCCTTC
AATGGGAA TCGTGAGGA TGCAGCCTTCAC ACTTTCCTCACGAAAGCCTACGA
CD164 NM_006016 369 CAACCTGTGC 370 ACACCCAAGA 371 CCTCCAATGAAA 372 CAACCTGTGCGAAAGTCTACCTTTGATGCAGCCAGTTTCATTG
GAAAGTCTAC CCAGGACAAT CTGGCTGCATCA GAGGAATTGTCCTGGTCTTGGGTGT
C
CD1A NM_001763 373 GGAGTGGAAG 374 TCATGGGCGT 375 CGCACCATTCGG 376 GGAGTGGAAGGAACTGGAAACATTATTCCGTATACGCACCATT
GAACTGGAAA ATCTACGAAT TCATTTGAGG CGGTCATTTGAGGGAATTCGTAGATACGCCCATGA
CD276 NM_ 377 CCAAAGGATG 378 GGATGACTTG 379 CCACTGTGCAGC 380 CCAAAGGATGCGATACACAGACCACTGTGCAGCCTTATTTCTC
001024736 CGATACACAG GGAATCATGT CTTATTTCTCCA CAATGGACATGATTCCCAAGTCATCC
C ATG
CD44 NM_000610 381 GGCACCACTG 382 GATGCTCATG 383 ACTGGAACCCAG 384 GGCACCACTGCTTATGAAGGAAACTGGAACCCAGAAGCACAC
CTTATGAAGG GTGAATGAGG AAGCACACCCTC CCTCCCCTCATTCACCATGAGCATC
CD68 NM_001251 385 TGGTTCCCAG 386 CTCCTCCACC 387 CTCCAAGCCCAG 388 TGGTTCCCAGCCCTGTGTCCACCTCCAAGCCCAGATTCAGATT
CCCTGTGT CTGGGTTGT ATTCAGATTCGA CGAGTCATGTACACAACCCAGGGTGGAGGAG
GTCA
CD82 NM_002231 389 GTGCAGGCTC 390 GACCTCAGGG 391 TCAGCTTCTACA 392 GTGCAGGCTCAGGTGAAGTGCTGCGGCTGGGTCAGCTTCTAC
AGGTGAAGTG CGATTCATGA ACTGGACAGACA AACTGGACAGACAACGCTGAGCTCATGAATCGCCCTGAGGTC
ACGCTG
CDC20 NM_001255 393 TGGATTGGAG 394 GCTTGCACTC 395 ACTGGCCGTGGC 396 TGGATTGGAGTTCTGGGAATGTACTGGCCGTGGCACTGGACA
TTCTGGGAAT CACAGGTACA ACTGGACAACA ACAGTGTGTACCTGTGGAGTGCAAGC
G CA
CDC25B NM_021873 397 GCTGCAGGAC 398 TAGGGCAGCT 399 CTGCTACCTCCC 400 GCTGCAGGACCAGTGAGGGGCCTGCGCCAGTCCTGCTACCTC
CAGTGAGG GGCTTCAG TTGCCTTTCGAG CCTTGCCTTTCGAGGCCTGAAGCCAGCTGCCCTA
CDC6 NM_001254 401 GCAACACTCC 402 TGAGGGGGAC 403 TTGTTCTCCACC 404 GCAACACTCCCCATTTACCTCCTTGTTCTCCACCAAAGCAAGG
CCATTTACCT CATTCTCTTT AAAGCAAGGCAA CAAGAAAGAGAATGGTCCCCCTCA
C
CDH1 NM_004360 405 TGAGTGTCCC 406 CAGCCGCTTT 407 TGCCAATCCCGA 408 TGAGTGTCCCCCGGTATCTTCCCCGCCCTGCCAATCCCGATGA
CCGGTATCTT CAGATTTTCA TGAAATTGGAAA AATTGGAAATTTTATTGATGAAAATCTGAAAGCGGCTG
C T TTT
CDH10 NM_006727 409 TGTGGTGCAA 410 TGTAAATGAC 411 ATGCCGATGACC 412 TGTGGTGCAAGTCACAGCTACAGATGCCGATGACCCTTCATAT
GTCACAGCTA TCTGGCGCTG CTTCATATGGGA GGGAACAGCGCCAGAGTCATTTACA
C
CDH11 NM_001797 413 GTCGGCAGAA 414 CTACTCATGG 415 CCTTCTGCCCAT 416 GTCGGCAGAAGCAGGACTTGTACCTTCTGCCCATAGTGATCAG
GCAGGACT GCGGGATG AGTGATCAGCGA CGATGGCGGCATCCCGCCCATGAGTAG
CDH19 NM_021153 417 AGTACCATAA 418 AGACTGCCTG 419 ACTCGGAAAACC 420 AGTACCATAATGCGGGAACGCAAGACTCGGAAAACCACAAGC
TGCGGGAACG TATAGGCTCC ACAAGCGCTGAG GCTGAGATCAGGAGCCTATACAGGCAGTCT
TG
CDH5 NM_001795 421 ACAGGAGACG 422 CAGCAGTGAG 423 TATTCTCCCGGT 424 ACAGGAGACGTGTTCGCCATTGAGAGGCTGGACCGGGAGAAT
TGTTCGCC GTGGTACTCT CCAGCCTCTCAA ATCTCAGAGTACCACCTCACTGCTG
GA
CDH7 NM_033646 425 GTTTGACATG 426 AGTCACATCC 427 ACCTCAACGTCA 428 GTTTGACATGGCTGCACTGAGAAACCTCAACGTCATCCGAGAC
GCTGCACTGA CTCCGGGT TCCGAGACACCA ACCAAGACCCGGAGGGATGTGACT
CDK14 NM_012395 429 GCAAGGTAAA 430 GATAGCTGTG 431 CTTCCTGCAGCC 432 GCAAGGTAAATGGGAAGTTGGTAGCTCTGAAGGTGATCAGGC
TGGGAAGTTG AAAGGTGTCC TGATCACCTTCA TGCAGGAAGAAGAAGGGACACCTTTCACAGCTATC
G CT
CDK2 NM_001798 433 AATGCTGCAC 434 TTGGTCACAT 435 CCTTGGCCGAAA 436 AATGCTGCACTACGACCCTAACAAGCGGATTTCGGCCAAGGC
TACGACCCTA CCTGGAAGAA TCCGCTTGT AGCCCTGGCTCACCCTTTCTTCCAGGATGTGACCAA
CDK3 NM_001258 437 CCAGGAAGGG 438 GTTGCATGAG 439 CTCTGGCTCCAG 440 CCAGGAAGGGACTGGAAGAGATTGTGCCCAATCTGGAGCCAG
ACTGGAAGA CAGGTCCC ATTGGGCACAAT AGGGCAGGGACCTGCTCATGCAAC
CDK7 NM_001799 441 GTCTCGGGCA 442 CTCTGGCCTT 443 CCTCCCCAAGGA 444 GTCTCGGGCAAAGCGTTATGAGAAGCTGGACTTCCTTGGGGA
AAGCGTTAT GTAAACGGTG AGTCCAGCTTCT GGGACAGTTTGCCACCGTTTACAAGGCCAGAG
CDKN1A NM_000389 445 TGGAGACTCT 446 GGCGTTTGGA 447 CGGCGGCAGACC 448 TGGAGACTCTCAGGGTCGAAAACGGCGGCAGACCAGCATGAC
CAGGGTCGAA GTGGTAGAAA AGCATGAC AGATTTCTACCACTCCAAACGCC
A TC
CDKN1C NM_000076 449 CGGCGATCAA 450 CAGGCGCTGA 451 CGGGCCTCTGAT 452 CGGCGATCAAGAAGCTGTCCGGGCCTCTGATCTCCGATTTCTT
GAAGCTGT TCTCTTGC CTCCGATTTCTT CGCCAAGCGCAAGAGATCAGCGCCTG
CDKN2B NM_004936 453 GACGCTGCAG 454 GCGGGAATCT 455 CACAGGATGCTG 456 GACGCTGCAGAGCACCTTTGCACAGGATGCTGGCCTTTGCTCT
AGCACCTT CTCCTCAGT GCCTTTGCTCTT TACTACACTGAGGAGAGATTCCCGC
CDKN2C NM_001262 457 GAGCACTGGG 458 CAAAGGCGAA 459 CCTGTAACTTGA 460 GAGCACTGGGCAATCGTTACGACCTGTAACTTGAGGGCCACC
CAATCGTTAC CGGGAGTAG GGGCCACCGAAC GAACTGCTACTCCCGTTCGCCTTTG
CDKN3 NM_005192 461 TGGATCTCTA 462 ATGTCAGGAG 463 ATCACCCATCAT 464 TGGATCTCTACCAGCAATGTGGAATTATCACCCATCATCATCC
CCAGCAATGT TCCCTCCATC CATCCAATCGCA AATCGCAGATGGAGGGACTCCTGACAT
G
CDS2 NM_003818 465 GGGCTTCTTT 466 ACAGGGCAGA 467 CCCGGACATCAC 468 GGGCTTCTTTGCTACTGTGGTGTTTGGCCTTCTGCTGTCCTAT
GCTACTGTGG CAAAGCATCT ATAGGACAGCAG GTGATGTCCGGGTACAGATGCTTTGTCTGCCCTGT
CENPF NM_016343 469 CTCCCGTCAA 470 GGGTGAGTCT 471 ACACTGGACCAG 472 CTCCCGTCAACAGCGTTCTTTCCAAACACTGGACCAGGAGTGC
CAGCGTTC GGCCTTCA GAGTGCATCCAG ATCCAGATGAAGGCCAGACTCACCC
CHAF1A NM_005483 473 GAACTCAGTG 474 GCTCTGTAGC 475 TGCACGTACCAG 476 GAACTCAGTGTATGAGAAGCGGCCTGACTTCAGGATGTGCTG
TATGAGAAGC ACCTGCGG CACATCCTGAAG GTACGTGCACCCGCAGGTGCTACAGAGC
GG
CHN1 NM_001822 477 TTACGACGCT 478 TCTCCCTGAT 479 CCACCATTGGCC 480 TTACGACGCTCGTGAAAGCACATACCACTAAGCGGCCAATGGT
CGTGAAAGC GCACATGTCT GCTTAGTGGTAT GGTAGACATGTGCATCAGGGAGA
CHRAC1 NM_017444 481 TCTCGCTGCC 482 CCTGGTTGAT 483 ATCCGGGTCATC 484 TCTCGCTGCCTCTATCCCGCATCCGGGTCATCATGAAGAGCTC
TCTATCCC GCTGGACA ATGAAGAGCTCC CCCCGAGGTGTCCAGCATCAACCAGG
CKS2 NM_001827 485 GGCTGGACGT 486 CGCTGCAGAA 487 CTGCGCCCGCTC 488 GGCTGGACGTGGTTTTGTCTGCTGCGCCCGCTCTTCGCGCTCT
GGTTTTGTCT AATGAAACGA TTCGCG CGTTTCATTTTCTGCAGCG
CLDN3 NM_001306 489 ACCAACTGCG 490 GGCGAGAAGG 491 CAAGGCCAAGAT 492 ACCAACTGCGTGCAGGACGACACGGCCAAGGCCAAGATCACC
TGCAGGAC AACAGCAC CACCATCGTGG ATCGTGGCAGGCGTGCTGTTCCTTCTCGCC
CLTC NM_004859 493 ACCGTATGGA 494 TGACTACAGG 495 TCTCACATGCTG 496 ACCGTATGGACAGCCACAGCCTGGCTTTGGGTACAGCATGTG
CAGCCACAG ATCAGCGCTT TACCCAAAGCCA AGATGAAGCGCTGATCCTGTAGTCA
C
COL11A1 NM_001854 497 GCCCAAGAGG 498 GGACCTGGGT 499 CTGCTCGACCTT 500 GCCCAAGAGGGGAAGATGGCCCTGAAGGACCCAAAGGTCGA
GGAAGATG CTCCAGTTG TGGGTCCTTCAG GCAGGCCCAACTGGAGACCCAGGTCC
COL1A1 NM_000088 501 GTGGCCATCC 502 CAGTGGTAGG 503 TCCTGCGCCTGA 504 GTGGCCATCCAGCTGACCTTCCTGCGCCTGATGTCCACCGAG
AGCTGACC TGATGTTCTG TGTCCACCG GCCTCCCAGAACATCACCTACCACTG
GGA
COL1A2 NM_000089 505 CAGCCAAGAA 506 AAACTGGCTG 507 TCTCCTAGCCAG 508 CAGCCAAGAACTGGTATAGGAGCTCCAAGGACAAGAAACACG
CTGGTATAGG CCAGCATTG ACGTGTTTCTTG TCTGGCTAGGAGAAACTATCAATGCTGGCAGCCAGTTT
AGCT TCCTTG
COL3A1 NM_000090 509 GGAGGTTCTG 510 ACCAGGACTG 511 CTCCTGGTCCCC 512 GGAGGTTCTGGACCTGCTGGTCCTCCTGGTCCCCAAGGTGTC
GACCTGCTG CCACGTTC AAGGTGTCAAAG AAAGGTGAACGTGGCAGTCCTGGT
COL4A1 NM_001845 513 ACAAAGGCCT 514 GAGTCCCAGG 515 CTCCTTTGACAC 516 ACAAAGGCCTCCCAGGATTGGATGGCATCCCTGGTGTCAAAG
CCCAGGAT AAGACCTGCT CAGGGATGCCAT GAGAAGCAGGTCTTCCTGGGACTC
COL5A1 NM_000093 517 CTCCCTGGGA 518 CTGGACCAGG 519 CCAGGGAAACCA 520 CTCCCTGGGAAAGATGGCCCTCCAGGATTACGTGGTTTCCCTG
AAGATGGC AAGCCCTC CGTAATCCTGGA GGGACCGAGGGCTTCCTGGTCCAG
COL5A2 NM_000393 521 GGTCGAGGAA 522 GCCTGGAGGT 523 CCAGGAAATCCT 524 GGTCGAGGAACCCAAGGTCCGCCTGGTGCTACAGGATTTCCT
CCCAAGGT CCAACTCTG GTAGCACCAGGC GGTTCTGCGGGCAGAGTTGGACCTCCAGGC
COL6A1 NM_001848 525 GGAGACCCTG 526 TCTCCAGGGA 527 CTTCTCTTCCCT 528 GGAGACCCTGGTGAAGCTGGCCCGCAGGGTGATCAGGGAAG
GTGAAGCTG CACCAACG GATCACCCTGCG AGAAGGCCCCGTTGGTGTCCCTGGAGA
COL6A3 NM_004369 529 GAGAGCAAGC 530 AACAGGGAAC 531 CCTCTTTGACGG 532 GAGAGCAAGCGAGACATTCTGTTCCTCTTTGACGGCTCAGCCA
GAGACATTCT TGGCCCAC CTCAGCCAATCT ATCTTGTGGGCCAGTTCCCTGTT
G
COL8A1 NM_001850 533 TGGTGTTCCA 534 CCCTGTAAAC 535 CCTAAGGGAGAG 536 TGGTGTTCCAGGGCTTCTCGGACCTAAGGGAGAGCCAGGAAT
GGGCTTCT CCTGATCCC CCAGGAATCCCA CCCAGGGGATCAGGGTTTACAGGG
COL9A2 NM_001852 537 GGGAACCATC 538 ATTCCGGGTG 539 ACACAGGAAATC 540 GGGAACCATCCAGGGTCTGGAAGGCAGTGCGGATTTCCTGTG
CAGGGTCT GACAGTTG CGCACTGCCTTC TCCAACCAACTGTCCACCCGGAAT
CRISP3 NM_006061 541 TCCCTTATGA 542 AACCATTGGT 543 TGCCAGTTGCCC 544 TCCCTTATGAACAAGGAGCACCTTGTGCCAGTTGCCCAGATAA
ACAAGGAGCA GCATAGTCCA AGATAACTGTGA CTGTGACGATGGACTATGCACCAATGGTT
C T
CSF1 NM_000757 545 TGCAGCGGCT 546 CAACTGTTCC 547 TCAGATGGAGAC 548 TGCAGCGGCTGATTGACAGTCAGATGGAGACCTCGTGCCAAA
GATTGACA TGGTCTACAA CTCGTGCCAAAT TTACATTTGAGTTTGTAGACCAGGAACAGTTG
ACTCA TACA
CSK NM_004383 549 CCTGAACATG 550 CATCACGTCT 551 TCCCGATGGTCT 552 CCTGAACATGAAGGAGCTGAAGCTGCTGCAGACCATCGGGAA
AAGGAGCTGA CCGAACTCC GCAGCAGCT GGGGGAGTTCGGAGACGTGATG
CSRP1 NM_004078 553 ACCCAAGACC 554 GCAGGGGTGG 555 CCACCCTTCTCC 556 ACCCAAGACCCTGCCTCTTCCACTCCACCCTTCTCCAGGGACC
CTGCCTCT AGTGATGT AGGGACCCTTAG CTTAGATCACATCACTCCACCCCTGC
CTGF NM_001901 557 GAGTTCAAGT 558 AGTTGTAATG 559 AACATCATGTTC 560 GAGTTCAAGTGCCCTGACGGCGAGGTCATGAAGAAGAACATG
GCCCTGACG GCAGGCACAG TTCTTCATGACC ATGTTCATCAAGACCTGTGCCTGCCATTACAACT
TCGC
CTHRC1 NM_138455 561 TGGCTCACTT 562 TCAGCTCCAT 563 CAACGCTGACAG 564 TGGCTCACTTCGGCTAAAATGCAGAAATGCATGCTGTCAGCGT
CGGCTAAAAT TGAATGTGAA CATGCATTTCTG TGGTATTTCACATTCAATGGAGCTGA
A
CTNNA1 NM_001903 565 CGTTCCGATC 566 AGGTCCCTGT 567 ATGCCTACAGCA 568 CGTTCCGATCCTCTATACTGCATCCCAGGCATGCCTACAGCAC
CTCTATACTG TGGCCTTATA CCCTGATGTCGC CCTGATGTCGCAGCCTATAAGGCCAACAGGGACCT
CAT GG A
CTNNB1 NM_001904 569 GGCTCTTGTG 570 TCAGATGACG 571 AGGCTCAGTGAT 572 GGCTCTTGTGCGTACTGTCCTTCGGGCTGGTGACAGGGAAGA
CGTACTGTCC AAGAGCACAG GTCTTCCCTGTC CATCACTGAGCCTGCCATCTGTGCTCTTCGTCATCTGA
TT ATG ACCAG
CTNND1 NM_001331 573 CGGAAACTTC 574 CTGAATCCTT 575 TTGATGCCCTCA 576 CGGAAACTTCGGGAATGTGATGGTTTAGTTGATGCCCTCATTT
GGGAATGTGA CTGCCCAATC TTTTCATTGTTC TCATTGTTCAGGCTGAGATTGGGCAGAAGGATTCAG
TC AGGC
CTNND2 NM_001332 577 GCCCGTCCCT 578 CTCACACCCA 579 CTATGAAACGAG 580 GCCCGTCCCTACAGTGAACTGAACTATGAAACGAGCCACTACC
ACAGTGAAC GGAGTCGG CCACTACCCGGC CGGCCTCCCCCGACTCCTGGGTGTGAG
CTSB NM_001908 581 GGCCGAGATC 582 GCAGGAAGTC 583 CCCCGTGGAGGG 584 GGCCGAGATCTACAAAAACGGCCCCGTGGAGGGAGCTTTCTC
TACAAAAACG CGAATACACA AGCTTTCTC TGTGTATTCGGACTTCCTGC
CTSD NM_001909 585 GTACATGATC 586 GGGACAGCTT 587 ACCCTGCCCGCG 588 GTACATGATCCCCTGTGAGAAGGTGTCCACCCTGCCCGCGAT
CCCTGTGAGA GTAGCCTTTG ATCACACTGA CACACTGAAGCTGGGAGGCAAAGGCTACAAGCTGTCCC
AGGT C
CTSK NM_000396 589 AGGCTTCTCT 590 CCACCTCTTC 591 CCCCAGGTGGTT 592 AGGCTTCTCTTGGTGTCCATACATATGAACTGGCTATGAACCA
TGGTGTCCAT ACTGGTCATG CATAGCCAGTTC CCTGGGGGACATGACCAGTGAAGAGGTGG
AC T
CTSL2 NM_001333 593 TGTCTCACTG 594 ACCATTGCAG 595 CTTGAGGACGCG 596 TGTCTCACTGAGCGAGCAGAATCTGGTGGACTGTTCGCGTCCT
AGCGAGCAGA CCCTGATTG AACAGTCCACCA CAAGGCAATCAGGGCTGCAATGGT
A
CTSS NM_004079 597 TGACAACGGC 598 TCCATGGCTT 599 TGATAACAAGGG 600 TGACAACGGCTTTCCAGTACATCATTGATAACAAGGGCATCGA
TTTCCAGTAC TGTAGGGATA CATCGACTCAGA CTCAGACGCTTCCTATCCCTACAAAGCCATGGA
AT GG CGCT
CUL1 NM_003592 601 ATGCCCTGGT 602 GCGACCACAA 603 CAGCCACAAAGC 604 ATGCCCTGGTAATGTCTGCATTCAACAATGACGCTGGCTTTGT
AATGTCTGCA GCCTTATCAA CAGCGTCATTGT GGCTGCTCTTGATAAGGCTTGTGGTCGC
T G
CXCL12 NM_000609 605 GAGCTACAGA 606 TTTGAGATGC 607 TTCTTCGAAAGC 608 GAGCTACAGATGCCCATGCCGATTCTTCGAAAGCCATGTTGCC
TGCCCATGC TTGACGTTGG CATGTTGCCAGA AGAGCCAACGTCAAGCATCTCAAA
CXCR4 NM_003467 609 TGACCGCTTC 610 AGGATAAGGC 611 CTGAAACTGGAA 612 TGACCGCTTCTACCCCAATGACTTGTGGGTGGTTGTGTTCCAG
TACCCCAATG CAACCATGAT CACAACCACCCA TTTCAGCACATCATGGTTGGCCTTATCCT
GT CAAG
CXCR7 NM_020311 613 CGCCTCAGAA 614 GTTGCATGGC 615 CTCAGAGCCAGG 616 CGCCTCAGAACGATGGATCTGCATCTCTTCGACTACTCAGAGC
CGATGGAT CAGCTGAT GAACTTCTCGGA CAGGGAACTTCTCGGACATCAGCTGGCCATGCAAC
CYP3A5 NM_000777 617 TCATTGCCCA 618 GACAGGCTTG 619 TCCCGCCTCAAG 620 TCATTGCCCAGTATGGAGATGTATTGGTGAGAAACTTGAGGCG
GTATGGAGAT CCTTTCTCTG TTTCTCACCAAT GGAAGCAGAGAAAGGCAAGCCTGTC
G
CYR61 NM_001554 621 TGCTCATTCT 622 GTGGCTGCAT 623 CAGCACCCTTGG 624 TGCTCATTCTTGAGGAGCATTAAGGTATTTCGAAACTGCCAAG
TGAGGAGCAT TAGTGTCCAT CAGTTTCGAAAT GGTGCTGGTGCGGATGGACACTAATGCAGCCAC
DAG1 NM_004393 625 GTGACTGGGC 626 ATCCCACTTG 627 CAAGTCAGAGTT 628 GTGACTGGGCTCATGCCTCCAAGTCAGAGTTTCCCTGGTGCC
TCATGCCT TGCTCCTGTC TCCCTGGTGCCC CCAGAGACAGGAGCACAAGTGGGAT
DAP NM_004394 629 CCAGCCTTTC 630 GACCAGGTCT 631 CTCACCAGCTGG 632 CCAGCCTTTCTGGTGCTGTTCTCCAGTTCACGTCTGCCAGCTG
TGGTGCTG GCCTCTGC CAGACGTGAACT GTGAGGGCAGAGGCAGACCTGGTC
DAPK1 NM_004938 633 CGCTGACATC 634 TCTCTTTCAG 635 TCATATCCAAAC 636 CGCTGACATCATGAATGTTCCTCGACCGGCTGGAGGCGAGTTT
ATGAATGTTC CAACGATGTG TCGCCTCCAGCC GGATATGACAAAGACACATCGTTGCTGAAAGAGA
CT TCTT G
DARC NM_002036 637 GCCCTCATTA 638 CAGACAGAAG 639 TCAGCGCCTGTG 640 GCCCTCATTAGTCCTTGGCTCTTATCTTGGAAGCACAGGCGCT
GTCCTTGGCT GGCTGGGAC CTTCCAAGATAA GACAGCCGTCCCAGCCCTTCTGTCTG
DDIT4 NM_019058 641 CCTGGCGTCT 642 CGAAGAGGAG 643 CTAGCCTTTGGG 644 CCTGGCGTCTGTCCTCACCATGCCTAGCCTTTGGGACCGCTTC
GTCCTCAC GTGGACGA ACCGCTTCTCGT TCGTCGTCGTCCACCTCCTCTTCG
DDR2 NM_ 645 CTATTACCGG 646 CCCAGCAAGA 647 AGTGCTCCCTAT 648 CTATTACCGGATCCAGGGCCGGGCAGTGCTCCCTATCCGCTG
001014796 ATCCAGGGC TACTCTCCCA CCGCTGGATGTC GATGTCTTGGGAGAGTATCTTGCTGGG
DES NM_001927 649 ACTTCTCACT 650 GCTCCACCTT 651 TGAACCAGGAGT 652 ACTTCTCACTGGCCGACGCGGTGAACCAGGAGTTTCTGACCA
GGCCGACG CTCGTTGGT TTCTGACCACGC CGCGCACCAACGAGAAGGTGGAGC
DHRS9 NM_005771 653 GGAGAAAGGT 654 CAGTCAGTGG 655 ATCAATAATGCT 656 GGAGAAAGGTCTCTGGGGTCTGATCAATAATGCTGGTGTTCCC
CTCTGGGGTC GAGCCAGC GGTGTTCCCGGC GGCGTGCTGGCTCCCACTGACTG
DHX9 NM_001357 657 GTTCGAACCA 658 TCCAGTTGGA 659 CCAAGGAACCAC 660 GTTCGAACCATCTCAGCGACAAAACCAAGTGGGTGTGGTTCCT
TCTCAGCGAC TTGTGGAGGT ACCCACTTGGTT TGGTCACCTCCACAATCCAACTGGA
DIAPH1 NM_005219 661 CAAGCAGTCA 662 AGTTTTGCTC 663 TTCTTCTGTCTC 664 CAAGCAGTCAAGGAGAACCAGAAGCGGCGGGAGACAGAAGA
AGGAGAACCA GCCTCATCTT CCGCCGCTTC AAAGATGAGGCGAGCAAAACT
DICER1 NM_177438 665 TCCAATTCCA 666 GGCAGTGAAG 667 AGAAAAGCTGTT 668 TCCAATTCCAGCATCACTGTGGAGAAAAGCTGTTTGTCTCCCC
GCATCACTGT GCGATAAAGT TGTCTCCCCAGC AGCATACTTTATCGCCTTCACTGCC
A
DIO2 NM_013989 669 CTCCTTTCAC 670 AGGAAGTCAG 671 ACTCTTCCACCA 672 CTCCTTTCACGAGCCAGCTGCCAGCCTTCCGCAAACTGGTGG
GAGCCAGC CCACTGAGGA GTTTGCGGAAGG AAGAGTTCTCCTCAGTGGCTGACTTCCT
DLC1 NM_006094 673 GATTCAGACG 674 CACCTCTTGC 675 AAAGTCCATTTG 676 GATTCAGACGAGGATGAGCCTTGTGCCATCAGTGGCAAATGG
AGGATGAGCC TGTCCCTTTG CCACTGATGGCA ACTTTCCAAAGGGACAGCAAGAGGTG
DLGAP1 NM_004746 677 CTGCTGAGCC 678 AGCCTGGAAG 679 CGCAGACCACCC 680 CTGCTGAGCCCAGTGGAGCACCACCCCGCAGACCACCCATAC
CAGTGGAG GAGTTCCG ATACTACACCCA TACACCCAGCGGAACTCCTTCCAGGCT
DLL4 NM_019074 681 CACGGAGGTA 682 AGAAGGAAGG 683 CTACCTGGACAT 684 CACGGAGGTATAAGGCAGGAGCCTACCTGGACATCCCTGCTC
TAAGGCAGGA TCCAGCCG CCCTGCTCAGCC AGCCCCGCGGCTGGACCTTCCTTCT
G
DNM3 NM_015569 685 CTTTCCCACC 686 AAGGACCTTC 687 CATATCGCTGAC 688 CTTTCCCACCCGGCTTACAGACATATCGCTGACCGAATGGGAA
CGGCTTAC TGCAGGTGTG CGAATGGGAACC CCCCACACCTGCAGAAGGTCCTT
DPP4 NM_001935 689 GTCCTGGGAT 690 GTACTCCCAC 691 CGGCTATTCCAC 692 GTCCTGGGATCGGGAAGTGGCGTGTTCAAGTGTGGAATAGCC
CGGGAAGT CGGGATACAG ACTTGAACACGC GTGGCGCCTGTATCCCGGTGGGAGTAC
DPT NM_001937 693 CACCTAGAAG 694 CAGTAGCTCC 695 TTCCTAGGAAGG 696 CACCTAGAAGCCTGCCCACGATTCCTAGGAAGGCTGGCAGAC
CCTGCCCAC CCAGGGTTC CTGGCAGACACC ACCCTGGAACCCTGGGGAGCTACTG
DUSP1 NM_004417 697 AGACATCAGC 698 GACAAACACC 699 CGAGGCCATTGA 700 AGACATCAGCTCCTGGTTCAACGAGGCCATTGACTTCATAGAC
TCCTGGTTCA CTTCCTCCAG CTTCATAGACTC TCCATCAAGAATGCTGGAGGAAGGGTGTTTGTC
CA
DUSP6 NM_001946 701 CATGCAGGGA 702 TGCTCCTACC 703 TCTACCCTATGC 704 CATGCAGGGACTGGGATTCGAGGACTTCCAGGCGCATAGGGT
CTGGGATT CTATCATTTG GCCTGGAAGTCC AGAACCAAATGATAGGGTAGGAGCA
G
DVL1 NM_004421 705 TCTGTCCCAC 706 TCAGACTGTT 707 CTTGGAGCAGCC 708 TCTGTCCCACCTGCTGCTGCCCCTTGGAGCAGCCTGCACCTTC
CTGCTGCT GCCGGATG TGCACCTTCTCT TCTCCTCCCATCCGGCAACAGTCTGA
DYNLL1 NM_ 709 GCCGCCTACC 710 GCCTGACTCC 711 ACCCACGTCAGT 712 GCCGCCTACCTCACAGACTTGTGAGCACTCACTGACGTGGGT
001037494 TCACAGAC AGCTCTCCT GAGTGCTCACAA AGCGCCCAGGGCCTGCGGGGCGCAGGAGAGCTGGAGTCAGG
C
EBNA1BP2 NM_006824 713 TGCGGCGAGA 714 GTGACAAGGG 715 CCCGCTCTCGGA 716 TGCGGCGAGATGGACACTCCCCCGCTCTCGGATTCGGAGTCG
TGGACACT ATTCATCGGA TTCGGAGTCG GAATCCGATGAATCCCTTGTCAC
TT
ECE1 NM_001397 717 ACCTTGGGAT 718 GGACCAGGAC 719 TCCACTCTCGAT 720 ACCTTGGGATCTGCCTCCAAGCTGGTGCAGGGTATCGAGAGT
CTGCCTCC CTCCATCTG ACCCTGCACCAG GGATTCCAGATGGAGGTCCTGGTCC
EDN1 NM_001955 721 TGCCACCTGG 722 TGGACCTAGG 723 CACTCCCGAGCA 724 TGCCACCTGGACATCATTTGGGTCAACACTCCCGAGCACGTTG
ACATCATTTG GCTTCCAAGT CGTTGTTCCGT TTCCGTATGGACTTGGAAGCCCTAGGTCCA
C
EDNRA NM_001957 725 TTTCCTCAAA 726 TTACACATCC 727 CCTTTGCCTCAG 728 TTTCCTCAAATTTGCCTCAAGATGGAAACCCTTTGCCTCAGGG
TTTGCCTCAA AACCAGTGCC GGCATCCTTTT CATCCTTTTGGCTGGCACTGGTTGGATGTGTAA
G
EFNB2 NM_004093 729 TGACATTATC 730 GTAGTCCCCG 731 CGGACAGCGTCT 732 TGACATTATCATCCCGCTAAGGACTGCGGACAGCGTCTTCTGC
ATCCCGCTAA CTGACCTTCT TCTGCCCTCACT CCTCACTACGAGAAGGTCAGCGGGGACTAC
GGA C
EGF NM_001963 733 CTTTGCCTTG 734 AAATACCTGA 735 AGAGTTTAACAG 736 CTTTGCCTTGCTCTGTCACAGTGAAGTCAGCCAGAGCAGGGCT
CTCTGTCACA CACCCTTATG CCCTGCTCTGGC GTTAAACTCTGTGAAATTTGTCATAAGGGTGTCAGGTATTT
GT ACAAATT TGACTT
EGR1 NM_001964 737 GTCCCCGCTG 738 CTCCAGCTTA 739 CGGATCCTTTCC 740 GTCCCCGCTGCAGATCTCTGACCCGTTCGGATCCTTTCCTCAC
CAGATCTCT GGGTAGTTGT TCACTCGCCCA TCGCCCACCATGGACAACTACCCTAAGCTGGAG
CCAT
EGR3 NM_004430 741 CCATGTGGAT 742 TGCCTGAGAA 743 ACCCAGTCTCAC 744 CCATGTGGATGAATGAGGTGTCTCCTTTCCATACCCAGTCTCA
GAATGAGGTG GAGGTGAGGT CTTCTCCCCACC CCTTCTCCCCACCCTACCTCACCTCTTCTCAGGCA
EIF2C2 NM_012154 745 GCACTGTGGG 746 ATGTTTGGTG 747 CGGGTCACATTG 748 GCACTGTGGGCAGATGAAGAGGAAGTACCGCGTCTGCAATGT
CAGATGAA ACTGGCGG CAGACACGGTAC GACCCGGCGGCCCGCCAGTCACCAAACAT
EIF2S3 NM_001415 749 CTGCCTCCCT 750 GGTGGCAAGT 751 TCTCGTGCTTCA 752 CTGCCTCCCTGATTCAAGTGATTCTCGTGCTTCAGCCTCCCAT
GATTCAAGTG GCCTGTAATA GCCTCCCATGTA GTAGCTGATATTACAGGCACTTGCCACC
TC
EIF3H NM_003756 753 CTCATTGCAG 754 GCCATGAAGA 755 CAGAACATCAAG 756 CTCATTGCAGGCCAGATAAACACTTACTGCCAGAACATCAAGG
GCCAGATAAA GCTTGCCTA GAGTTCACTGCC AGTTCACTGCCCAAAACTTAGGCAAGCTCTTCATGGC
CA
EIF4E NM_001968 757 GATCTAAGAT 758 TTAGATTCCG 759 ACCACCCCTACT 760 GATCTAAGATGGCGACTGTCGAACCGGAAACCACCCCTACTC
GGCGACTGTC TTTTCTCCTC CCTAATCCCCCG CTAATCCCCCGACTACAGAAGAGGAGAAAACGGAATCTAA
GAA TTCTG ACT
EIF5 NM_001969 761 GAATTGGTCT 762 TCCAGGTATA 763 CCACTTGCACCC 764 GAATTGGTCTCCAGCTGCCTTTGATCAAGATTCGGGTGCAAGT
CCAGCTGCC TGGCTCCTGC GAATCTTGATCA GGAGCAGGAGCCATATACCTGGA
ELK4 NM_001973 765 GATGTGGAGA 766 AGTCATTGCG 767 ATAAACCACCTC 768 GATGTGGAGAATGGAGGGAAAGATAAACCACCTCAGCCTGGT
ATGGAGGGAA GCTAGAGGTC AGCCTGGTGCCA GCCAAGACCTCTAGCCGCAATGACT
ENPP2 NM_006209 769 CTCCTGCGCA 770 TCCCTGGATA 771 TAACTTCCTCTG 772 CTCCTGCGCACTAATACCTTCAGGCCAACCATGCCAGAGGAA
CTAATACCTT ATTGGGTCTG GCATGGTTGGCC GTTACCAGACCCAATTATCCAGGGA
C
ENY2 NM_020189 773 CCTCAAAGAG 774 CCTCTTTACA 775 CTGATCCTTCCA 776 CCTCAAAGAGTTGCTGAGAGCTAAATTAATTGAATGTGGCTGG
TTGCTGAGAG GTGTGCCTTC GCCACATTCAAT AAGGATCAGTTGAAGGCACACTGTAAAGAGG
C A TAATTT
EPHA2 NM_004431 777 CGCCTGTTCA 778 GTGGCGTGCC 779 TGCGCCCGATGA 780 CGCCTGTTCACCAAGATTGACACCATTGCGCCCGATGAGATCA
CCAAGATTGA TCGAAGTC GATCACCG CCGTCAGCAGCGACTTCGAGGCACGCCAC
C
EPHA3 NM_005233 781 CAGTAGCCTC 782 TTCGTCCCAT 783 TATTCCAAATCC 784 CAGTAGCCTCAAGCCTGACACTATATACGTATTCCAAATCCGA
AAGCCTGACA ATCCAGCG GAGCCCGAACAG GCCCGAACAGCCGCTGGATATGGGACGAA
EPHB2 NM_004442 785 CAACCAGGCA 786 GTAATGCTGT 787 CACCTGATGCAT 788 CAACCAGGCAGCTCCATCGGCAGTGTCCATCATGCATCAGGT
GCTCCATC CCACGGTGC GATGGACACTGC GAGCCGCACCGTGGACAGCATTAC
EPHB4 NM_004444 789 TGAACGGGGT 790 AGGTACCTCT 791 CGTCCCATTTGA 792 TGAACGGGGTATCCTCCTTAGCCACGGGGCCCGTCCCATTTG
ATCCTCCTTA CGGTCAGTGG GCCTGTCAATGT AGCCTGTCAATGTCACCACTGACCGAGAGGTACCT
ERBB2 NM_004448 793 CGGTGTGAGA 794 CCTCTCGCAA 795 CCAGACCATAGC 796 CGGTGTGAGAAGTGCAGCAAGCCCTGTGCCCGAGTGTGCTAT
AGTGCAGCAA GTGCTCCAT ACACTCGGGCAC GGTCTGGGCATGGAGCACTTGCGAGAGG
ERBB3 NM_001982 797 CGGTTATGTC 798 GAACTGAGAC 799 CCTCAAAGGTAC 800 CGGTTATGTCATGCCAGATACACACCTCAAAGGTACTCCCTCC
ATGCCAGATA CCACTGAAGA TCCCTCCTCCCG TCCCGGGAAGGCACCCTTTCTTCAGTGGGTCTCAGTTC
CAC AAGG G
ERBB4 NM_005235 801 TGGCTCTTAA 802 CAAGGCATAT 803 TGTCCCACGAAT 804 TGGCTCTTAATCAGTTTCGTTACCTGCCTCTGGAGAATTTACG
TCAGTTTCGT CGATCCTCAT AATGCGTAAATT CATTATTCGTGGGACAAAACTTTATGAGGATCGATATGCCTTG
TACCT AAAGT CTCCAG
ERCC1 NM_001983 805 GTCCAGGTGG 806 CGGCCAGGAT 807 CAGCAGGCCCTC 808 GTCCAGGTGGATGTGAAAGATCCCCAGCAGGCCCTCAAGGAG
ATGTGAAAGA ACACATCTTA AAGGAGCTG CTGGCTAAGATGTGTATCCTGGCCG
EREG NM_001432 809 TGCTAGGGTA 810 TGGAGACAAG 811 TAAGCCATGGCT 812 TGCTAGGGTAAACGAAGGCATAATAAGCCATGGCTGACCTCTG
AACGAAGGCA TCCTGGCAC GACCTCTGGAGC GAGCACCAGGTGCCAGGACTTGTCTCCA
ERG NM_004449 813 CCAACACTAG 814 CCTCCGCCAG 815 AGCCATATGCCT 816 CCAACACTAGGCTCCCCACCAGCCATATGCCTTCTCATCTGGG
GCTCCCCA GTCTTTAGT TCTCATCTGGGC CACTTACTACTAAAGACCTGGCGGAGG
ESR1 NM_000125 817 CGTGGTGCCC 818 GGCTAGTGGG 819 CTGGAGATGCTG 820 CGTGGTGCCCCTCTATGACCTGCTGCTGGAGATGCTGGACGC
CTCTATGAC CGCATGTAG GACGCCC CCACCGCCTACATGCGCCCACTAGCC
ESR2 NM_001437 821 TGGTCCATCG 822 TGTTCTAGCG 823 ATCTGTATGCGG 824 TGGTCCATCGCCAGTTATCACATCTGTATGCGGAACCTCAAAA
CCAGTTATCA ATCTTGCTTC AACCTCAAAAGA GAGTCCCTGGTGTGAAGCAAGATCGCTAGAACA
ACA GTCCCT
ETV1 NM_004956 825 TCAAACAAGA 826 AACTGCCAGA 827 ATCGGGAAGGAC 828 TCAAACAAGAGCCAGGAATGTATCGGGAAGGACCCACATACC
GCCAGGAATG GCTGAAGTGA CCACATACCAAC AACGGCGAGGATCACTTCAGCTCTGGCAGTT
ETV4 NM_001986 829 TCCAGTGCCT 830 ACTGTCCAAG 831 CAGACAAATCGC 832 TCCAGTGCCTATGACCCCCCCAGACAAATCGCCATCAAGTCCC
ATGACCCC GGCACCAG CATCAAGTCCCC CTGCCCCTGGTGCCCTTGGACAGT
EZH2 NM_004456 833 TGGAAACAGC 834 CACCGAACAC 835 TCCTGACTTCTG 836 TGGAAACAGCGAAGGATACAGCCTGTGCACATCCTGACTTCTG
GAAGGATACA TCCCTAGTCC TGAGCTCATTGC TGAGCTCATTGCGCGGGACTAGGGAGTGTTCGGTG
G
F2R NM_001992 837 AAGGAGCAAA 838 GCAGGGTTTC 839 CCCGGGCTCAAC 840 AAGGAGCAAACCATCCAGGTGCCCGGGCTCAACATCACTACC
CCATCCAGG ATTGAGCAC ATCACTACCTGT TGTCATGATGTGCTCAATGAAACCCTGC
FAAH NM_001441 841 GACAGCGTAG 842 AGCTGAACAT 843 TGCCCTTCGTGC 844 GACAGCGTAGTGGTGCATGTGCTGAAGCTGCAGGGTGCCGTG
TGGTGCATGT GGACTGTGGA ACACCAATG CCCTTCGTGCACACCAATGTTCCACAGTCCATGTTCAGCT
FABP5 NM_001444 845 GCTGATGGCA 846 CTTTCCTTCC 847 CCTGATGCTGAA 848 GCTGATGGCAGAAAAACTCAGACTGTCTGCAACTTTACAGATG
GAAAAACTCA CATCCCACT CCAATGCACCAT GTGCATTGGTTCAGCATCAGGAGTGGGATGGGAAGGAAAG
FADD NM_003824 849 GTTTTCGCGA 850 CTCCGGTGCC 851 AACGCGCTCTTG 852 GTTTTCGCGAGATAACGGTCGAAAACGCGCTCTTGTCGATTTC
GATAACGGTC TGATTCAC TCGATTTCCTGT CTGTAGTGAATCAGGCACCGGAG
FAM107A NM_007177 853 AAGTCAGGGA 854 GCTGGCCCTA 855 AATTGCCACACT 856 AAGTCAGGGAAAACCTGCGGAGAATTGCCACACTGACCAGCG
AAACCTGCG CAGCTCTCT GACCAGCGAAGA AAGAGAGAGAGCTGTAGGGCCAGC
FAM13C NM_198215 857 ATCTTCAAAG 858 GCTGGATACC 859 TCCTGACTTTCT 860 ATCTTCAAAGCGGAGAGCGGGAGGAGCCACGGAGAAAGTCAG
CGGAGAGCG ACATGCTCTG CCGTGGCTCCTC GAGACAGAGCATGTGGTATCCAGC
FAM171B NM_177454 861 CCAGGAAGGA 862 GTGGTCTGCC 863 TGAAGATTTTGA 864 CCAGGAAGGAAAAGCACTGTTGAAGATTTTGAAGCTAATACAT
AAAGCACTGT CCTTCTTTTA AGCTAATACATC CCCCCACTAAAAGAAGGGGCAGACCAC
CCCCAC
FAM49B NM_016623 865 AGATGCAGAA 866 GCTGGATTGC 867 TGGCCAGCTCCT 868 AGATGCAGAAGGCATCTTGGAGGACTTGCAGTCATACAGAGG
GGCATCTTGG CTCTCGTATT CTGTATGACTGC AGCTGGCCACGAAATACGAGAGGCAATCCAGC
FAM73A NM_198549 869 TGAGAAGGTG 870 GGCCATTAAA 871 AAGACCTCATGC 872 TGAGAAGGTGCGCTATTCAAGTACAGAGACTTTAGCTGAAGAC
CGCTATTCAA AGCTCAGTGC AGTTACTCATTC CTCATGCAGTTACTCATTCGCCGCACTGAGCTTTTAATGGCC
GCC
FAP NM_004460 873 GTTGGCTCAC 874 GACAGGACCG 875 AGCCACTGCAAA 876 GTTGGCTCACGTGGGTTACTGATGAACGAGTATGTTTGCAGTG
GTGGGTTAC AAACATTCTG CATACTCGTTCA GCTAAAAAGAGTCCAGAATGTTTCGGTCCTGTC
TCA
FAS NM_000043 877 GGATTGCTCA 878 GGCATTAACA 879 TCTGGACCCTCC 880 GGATTGCTCAACAACCATGCTGGGCATCTGGACCCTCCTACCT
ACAACCATGC CTTTTGGACG TACCTCTGGTTC CTGGTTCTTACGTCTGTTGCTAGATTATCGTCCAAAAGTGTTA
T ATAA TTACGT ATGCC
FASLG NM_000639 881 GCACTTTGGG 882 GCATGTAAGA 883 ACAACATTCTCG 884 GCACTTTGGGATTCTTTCCATTATGATTCTTTGTTACAGGCAC
ATTCTTTCCA AGACCCTCAC GTGCCTGTAACA CGAGAATGTTGTATTCAGTGAGGGTCTTCTTACATGC
TTAT TGAA AAGAA
FASN NM_004104 885 GCCTCTTCCT 886 GCTTTGCCCG 887 TCGCCCACCTAC 888 GCCTCTTCCTGTTCGACGGCTCGCCCACCTACGTACTGGCCTA
GTTCGACG GTAGCTCT GTACTGGCCTAC CACCCAGAGCTACCGGGCAAAGC
FCGR3A NM_000569 889 GTCTCCAGTG 890 AGGAATGCAG 891 CCCATGATCTTC 892 GTCTCCAGTGGAAGGGAAAAGCCCATGATCTTCAAGCAGGGA
GAAGGGAAAA CTACTCACTG AAGCAGGGAAGC AGCCCCAGTGAGTAGCTGCATTCCT
G
FGF10 NM_004465 893 TCTTCCGTCC 894 AGAGTTGGTG 895 ACACCATGTCCT 896 TCTTCCGTCCCTGTCACCTGCCAAGCCCTTGGTCAGGACATGG
CTGTCACCT GCCTCTGGT GACCAAGGGCTT TGTCACCAGAGGCCACCAACTCT
FGF17 NM_003867 897 GGTGGCTGTC 898 TCTAGCCAGG 899 TTCTCGGATCTC 900 GGTGGCTGTCCTCAAAATCTGCTTCTCGGATCTCCCTCAGTCT
CTCAAAATCT AGGAGTTTGG CCTCAGTCTGCC GCCCCCAGCCCCCAAACTCCTCCTGGCTAGA
FGF5 NM_004464 901 GCATCGGTTT 902 AACATATTGG 903 CCATTGACTTTG 904 GCATCGGTTTCCATCTGCAGATCTACCCGGATGGCAAAGTCAA
CCATCTGC CTTCGTGGGA CCATCCGGGTAG TGGATCCCACGAAGCCAATATGTT
FGF6 NM_020996 905 GGGCCATTAA 906 CCCGGGACAT 907 CATCCACCTTGC 908 GGGCCATTAATTCTGACCACGTGCCTGAGAGGCAAGGTGGAT
TTCTGACCAC AGTGATGAA CTCTCAGGCAC GGCCCTGGGACAGAAACTGTTCATCACTATGTCCCGGG
FGF7 NM_002009 909 CCAGAGCAAA 910 TCCCCTCCTT 911 CAGCCCTGAGCG 912 CCAGAGCAAATGGCTACAAATGTGAACTGTTCCAGCCCTGAGC
TGGCTACAAA CCATGTAATC ACACACAAGAAG GACACACAAGAAGTTATGATTACATGGAAGGAGGGGA
FGFR2 NM_000141 913 GAGGGACTGT 914 GAGTGAGAAT 915 TCCCAGAGACCA 916 GAGGGACTGTTGGCATGCAGTGCCCTCCCAGAGACCAACGTT
TGGCATGCA TCGATCCAAG ACGTTCAAGCAG CAAGCAGTTGGTAGAAGACTTGGATCGAATTCTCACTC
TCTTC TTG
FGFR4 NM_002011 917 CTGGCTTAAG 918 ACGAGACTCC 919 CCTTTCATGGGG 920 CTGGCTTAAGGATGGACAGGCCTTTCATGGGGAGAACCGCAT
GATGGACAGG AGTGCTGATG AGAACCGCATT TGGAGGCATTCGGCTGCGCCATCAGCACTGGAGTCTCGT
FKBP5 NM_004117 921 CCCACAGTAG 922 GGTTCTGGCT 923 TCTCCCCAGTTC 924 CCCACAGTAGAGGGGTCTCATGTCTCCCCAGTTCCACAGCAG
AGGGGTCTCA TTCACGTCTG CACAGCAGTGTC TGTCACAGACGTGAAAGCCAGAACC
FLNA NM_001456 925 GAACCTGCGG 926 GAAGACACCC 927 TACCAGGCCCAT 928 GAACCTGCGGTGGACACTTCCGGTGTCCAGTGCTATGGGCCT
TGGACACT TGGCCCTC AGCACTGGACAC GGTATTGAGGGCCAGGGTGTCTTC
FLNC NM_001458 929 CAGGACAATG 930 TGATGGTGTA 931 ATGTGCTGTCAG 932 CAGGACAATGGTGATGGCTCATGTGCTGTCAGCTACCTGCCCA
GTGATGGCT CTCGCCAGG CTACCTGCCCAC CGGAGCCTGGCGAGTACACCATCA
FLT1 NM_002019 933 GGCTCCTGAA 934 TCCCACAGCA 935 CTACAGCACCAA 936 GGCTCCTGAATCTATCTTTGACAAAATCTACAGCACCAAGAGC
TCTATCTTTG ATACTCCGTA GAGCGACGTGTG GACGTGTGGTCTTACGGAGTATTGCTGTGGGA
FLT4 NM_002020 937 ACCAAGAAGC 938 CCTGGAAGCT 939 AGCCCGCTGACC 940 ACCAAGAAGCTGAGGACCTGTGGCTGAGCCCGCTGACCATGG
TGAGGACCTG GTAGCAGACA ATGGAAGATCT AAGATCTTGTCTGCTACAGCTTCCAGG
FN1 NM_002026 941 GGAAGTGACA 942 ACACGGTAGC 943 ACTCTCAGGCGG 944 GGAAGTGACAGACGTGAAGGTCACCATCATGTGGACACCGCC
GACGTGAAGG CGGTCACT TGTCCACATGAT TGAGAGTGCAGTGACCGGCTACCGTGT
T
FOS NM_005252 945 CGAGCCCTTT 946 GGAGCGGGCT 947 TCCCAGCATCAT 948 CGAGCCCTTTGATGACTTCCTGTTCCCAGCATCATCCAGGCCC
GATGACTTCC GTCTCAGA CCAGGCCCAG AGTGGCTCTGAGACAGCCCGCTCC
T
FOXO1 NM_002015 949 GTAAGCACCA 950 GGGGCAGAGG 951 TATGAACCGCCT 952 GTAAGCACCATGCCCCACACCTCGGGTATGAACCGCCTGACC
TGCCCCAC CACTTGTA GACCCAAGTGAA CAAGTGAAGACACCTGTACAAGTGCCTCTGCCCC
FOXP3 NM_014009 953 CTGTTTGCTG 954 GTGGAGGAAC 955 TGTTTCCATGGC 956 CTGTTTGCTGTCCGGAGGCACCTGTGGGGTAGCCATGGAAAC
TCCGGAGG TCTGGGAATG TACCCCACAGGT AGCACATTCCCAGAGTTCCTCCAC
FOXQ1 NM_033260 957 TGTTTTTGTC 958 TGGAAAGGTT 959 TGATTTATGTCC 960 TGTTTTTGTCGCAACTTCCATTGATTTATGTCCCTTCCCTCCC
GCAACTTCCA CCCTGATGTA CTTCCCTCCCCC CCCTAAGTACATCAGGGAACCTTTCCA
CT
FSD1 NM_024333 961 AGGCCTCCTG 962 TGTGTGAACC 963 CGCACCAAACAA 964 AGGCCTCCTGTCCTTCTACAATGCCCGCACCAAACAAGTGCTG
TCCTTCTACA TGGTCTTGAA GTGCTGCACA CACACTTTCAAGACCAGGTTCACACA
A
FYN NM_002037 965 GAAGCGCAGA 966 CTCCTCAGAC 967 CTGAAGCACGAC 968 GAAGCGCAGATCATGAAGAAGCTGAAGCACGACAAGCTGGTC
TCATGAAGAA ACCACTGCAT AAGCTGGTCCAG CAGCTCTATGCAGTGGTGTCTGAGGAG
G6PD NM_000402 969 AATCTGCCTG 970 CGAGATGTTG 971 CCAGCCTCAGTG 972 AATCTGCCTGTGGCCTTGCCCGCCAGCCTCAGTGCCACTTGA
TGGCCTTG CTGGTGACA CCACTTGACATT CATTCCTTGTCACCAGCAACATCTCG
GABRG2 NM_198904 973 CCACTGTCCT 974 GAGATCCATC 975 CTCAGCACCATT 976 CCACTGTCCTGACAATGACCACCCTCAGCACCATTGCCCGGA
GACAATGACC GCTGTGACAT GCCCGGAAAT AATCGCTCCCCAAGGTCTCCTATGTCACAGCGATGGATCTC
GADD45A NM_001924 977 GTGCTGGTGA 978 CCCGGCAAAA 979 TTCATCTCAATG 980 GTGCTGGTGACGAATCCACATTCATCTCAATGGAAGGATCCTG
CGAATCCA ACAAATAAGT GAAGGATCCTGC CCTTAAGTCAACTTATTTGTTTTTGCCGGG
C
GADD45B NM_015675 981 ACCCTCGACA 982 TGGGAGTTCA 983 TGGGAGTTCATG 984 ACCCTCGACAAGACCACACTTTGGGACTTGGGAGCTGGGGCT
AGACCACACT TGGGTACAGA GGTACAGA GAAGTTGCTCTGTACCCATGAACTCCCA
GDF15 NM_004864 985 CGCTCCAGAC 986 ACAGTGGAAG 987 TGTTAGCCAAAG 988 CGCTCCAGACCTATGATGACTTGTTAGCCAAAGACTGCCACTG
CTATGATGAC GACCAGGACT ACTGCCACTGCA CATATGAGCAGTCCTGGTCCTTCCACTGT
T
GHR NM_000163 989 CCACCTCCCA 990 GGTGCGTGCC 991 CGTGCCTCAGCC 992 CCACCTCCCACAGGTTCAGGCGATTCCCGTGCCTCAGCCTCC
CAGGTTCA TGTAGTCC TCCTGAGTAGCT TGAGTAGCTGGGACTACAGGCACGCACC
GNPTAB NM_024312 993 GGATTCACAT 994 GTTCTTGCAT 995 CCCTGCTCACAT 996 GGATTCACATCGCGGAAAGTCCCTGCTCACATGCCTCACATGA
CGCGGAAA AACAATCCGG GCCTCACATGAT TTGACCGGATTGTTATGCAAGAAC
TC
GNRH1 NM_000825 997 AAGGGCTAAA 998 CTGGATCTCT 999 TCCTGTCCTTCA 1000 AAGGGCTAAATCCAGGTGTGACGGTATCTAATGATGTCCTGTC
TCCAGGTGTG GTGGCTGGT CTGTCCTTGCCA CTTCACTGTCCTTGCCATCACCAGCCACAGAGATCCAG
GPM6B NM_ 1001 ATGTGCTTGG 1002 TGTAGAACAT 1003 CGCTGAGAAACC 1004 ATGTGCTTGGAGTGGCCTGGCTGGGTGTGTTTGGTTTCTCAGC
001001994 AGTGGCCT AAACACGGGC AAACACACCCAG GGTGCCCGTGTTTATGTTCTACA
A
GPNMB NM_ 1005 CAGCCTCGCC 1006 TGACAAATAT 1007 CAAACAGTGCCC 1008 CAGCCTCGCCTTTAAGGATGGCAAACAGTGCCCTGATCTCCGT
001005340 TTTTAAGGA GGCCAAGCAG TGATCTCCGTTG TGGCTGCTTGGCCATATTTGTCA
GPR68 NM_003485 1009 CAAGGACCAG 1010 GGTAGGGCAG 1011 CTCAGCACCGTG 1012 CAAGGACCAGATCCAGCGGCTGGTGCTCAGCACCGTGGTCAT
ATCCAGCG GAAGCAGG GTCATCTTCCTG CTTCCTGGCCTGCTTCCTGCCCTACC
GPS1 NM_004127 1013 AGTACAAGCA 1014 GCAGCTCAGG 1015 CCTCCTGCTGGC 1016 AGTACAAGCAGGCTGCCAAGTGCCTCCTGCTGGCTTCCTTTGA
GGCTGCCAAG GAAGTCACA TTCCTTTGATCA TCACTGTGACTTCCCTGAGCTGC
GRB7 NM_005310 1017 CCATCTGCAT 1018 GGCCACCAGG 1019 CTCCCCACCCTT 1020 CCATCTGCATCCATCTTGTTTGGGCTCCCCACCCTTGAGAAGT
CCATCTTGTT GTATTATCTG GAGAAGTGCCT GCCTCAGATAATACCCTGGTGGCC
GREM1 NM_013372 1021 GTGTGGGCAA 1022 GACCTGATTT 1023 TCCACCCTCCCT 1024 GTGTGGGCAAGGACAAGCAGGATAGTGGAGTGAGAAAGGGAG
GGACAAGC GGCCTCACC TTCTCACTCCAC GGTGGAGGGTGAGGCCAAATCAGGTC
GSK3B NM_002093 1025 GACAAGGACG 1026 TTGTGGCCTG 1027 CCAGGAGTTGCC 1028 GACAAGGACGGCAGCAAGGTGACAACAGTGGTGGCAACTCCT
GCAGCAAG TCTGGACC ACCACTGTTGTC GGGCAGGGTCCAGACAGGCCACAA
GSN NM_000177 1029 CTTCTGCTAA 1030 GGCTCAAAGC 1031 ACCCAGCCAATC 1032 CTTCTGCTAAGCGGTACATCGAGACGGACCCAGCCAATCGGG
GCGGTACATC CTTGCTTCAC GGGATCGGC ATCGGCGGACGCCCATCACCGTGGTGAAGCAAGGCTTTGAGC
GA C
GSTM1 NM_000561 1033 AAGCTATGAG 1034 GGCCCAGCTT 1035 TCAGCCACTGGC 1036 AAGCTATGAGGAAAAGAAGTACACGATGGGGGACGCTCCTGA
GAAAAGAAGT GAATTTTTCA TTCTGTCATAAT TTATGACAGAAGCCAGTGGCTGAATGAAAAATTCAAGCTGGGC
ACACGAT CAGGAG C
GSTM2 NM_000848 1037 CTGCAGGCAC 1038 CCAAGAAACC 1039 CTGAAGCTCTAC 1040 CTGCAGGCACTCCCTGAAATGCTGAAGCTCTACTCACAGTTTC
TCCCTGAAAT ATGGCTGCTT TCACAGTTTCTG TGGGGAAGCAGCCATGGTTTCTTGG
GG
HDAC1 NM_004964 1041 CAAGTACCAC 1042 GCTTGCTGTA 1043 TTCTTGCGCTCC 1044 CAAGTACCACAGCGATGACTACATTAAATTCTTGCGCTCCATC
AGCGATGACT CTCCGACATG ATCCGTCCAGA CGTCCAGATAACATGTCGGAGTACAGCAAGC
ACATTAA TT
HDAC9 NM_178423 1045 AACCAGGCAG 1046 CTCTGTCTTC 1047 CCCCCTGAAGCT 1048 AACCAGGCAGTCACCTTGAGGAAGCAGAGGAAGAGCTTCAGG
TCACCTTGAG CTGCATCGC CTTCCTCTGCTT GGGACCAGGCGATGCAGGAAGACAGAG
HGD NM_000187 1049 CTCAGGTCTG 1050 TTATTGGTGC 1051 CTGAGCAGCTCT 1052 CTCAGGTCTGCCCCTACAATCTCTATGCTGAGCAGCTCTCAGG
CCCCTACAAT TCCGTGGAC CAGGATCGGCTT ATCGGCTTTCACTTGTCCACGGAGCACCAATAA
HIP1 NM_005338 1053 CTCAGAGCCC 1054 GGGTTTCCCT 1055 CGACTCACTGAC 1056 CTCAGAGCCCCACCTGAGCCTGCCGACTCACTGACCGAGGCC
CACCTGAG GCCATACTG CGAGGCCTGTAA TGTAAGCAGTATGGCAGGGAAACCC
HIRIP3 NM_003609 1057 GGATGAGGAA 1058 TCCCTAGCTG 1059 CCATTGCTCCTG 1060 GGATGAGGAAAAGGGGGATTGGAAACCCAGAACCAGGAGCAA
AAGGGGGAT ACTTTCTCCG GTTCTGGGTTTC TGGCCGGAGAAAGTCAGCTAGGGA
HK1 NM_000188 1061 TACGCACAGA 1062 GAGAGAAGTG 1063 TAAGAGTCCGGG 1064 TACGCACAGAGGCAAGCAGCTAAGAGTCCGGGATCCCCAGCC
GGCAAGCA CTGGAGAGGC ATCCCCAGCCTA TACTGCCTCTCCAGCACTTCTCTC
HLA-G NM_002127 1065 CCATCCCCAT 1066 CCGCAGCTCC 1067 CTGCAAGGACAA 1068 CCTGCGCGGCTACTACAACCAGAGCGAGGCCAGTTCTCACAC
CATGGGTATC AGTGACTACA CCAGGCCAGCAA CCTCCAGTGGATGATTGGCTGCGACCTG
HLF NM_002126 1069 CACCCTGCAG 1070 GGTACCTAGG 1071 TAAGTGATCTGC 1072 CACCCTGCAGGTGTCTGAGACTAAGTGATCTGCCCTCCAGGT
GTGTCTGAG AGCAGAAGGT CCTCCAGGTGGC GGCGATCACCTTCTGCTCCTAGGTACC
GA
HNF1B NM_000458 1073 TCCCAGCATC 1074 CGTACCAGGT 1075 CCCCTATGAAGA 1076 TCCCAGCATCTCAACAAGGGCACCCCTATGAAGACCCAGAAG
TCAACAAGG GTACAGAGCG CCCAGAAGCGTG CGTGCCGCTCTGTACACCTGGTACG
HPS1 NM_000195 1077 GCGGAAGCTG 1078 TTCGGATAAG 1079 CAGTCACCAGCC 1080 GCGGAAGCTGTATGTGCTCAAGTACCTGTTTGAAGTGCACTTT
TATGTGCTC ATGACCGTCC CAAAGTGCACTT GGGCTGGTGACTGTGGACGGTCATCTTATCCGAA
HRAS NM_005343 1081 GGACGAATAC 1082 GCACGTCTCC 1083 ACCACCTGCTTC 1084 GGACGAATACGACCCCACTATAGAGGATTCCTACCGGAAGCA
GACCCCACT CCATCAAT CGGTAGGAATCC GGTGGTCATTGATGGGGAGACGTGC
HSD17B10 NM_004493 1085 CCAGCGAGTT 1086 ATCTCACCAG 1087 TCATGGGCACCT 1088 CCACCAGACAAGACCGATTCGCTGGCCTCCATTTCTTCAACCC
CTTGATGTGA CCACCAGG TCAATGTGATCC AGTGCCTGTCATGAAACTTGTGG
HSD17B2 NM_002153 1089 GCTTTCCAAG 1090 TGCCTGCGAT 1091 AGTTGCTTCCAT 1092 GCTTTCCAAGTGGGGAATTAAAGTTGCTTCCATCCAACCTGGA
TGGGGAATTA ATTTGTTAGG CCAACCTGGAGG GGCTTCCTAACAAATATCGCAGGCA
HSD17B3 NM_000197 1093 GGGACGTCCT 1094 TGGAGAATCT 1095 CTTCATCCTCAC 1096 GGGACGTCCTGGAACAGTTCTTCATCCTCACAGGGCTGCTGG
GGAACAGT CACGCACTTC AGGGCTGCTGGT TGTGCCTGGCCTGCCTGGCGAAGTGCGTGAGATTCTCCA
HSD17B4 NM_000414 1097 CGGGAAGCTT 1098 ACCTCAGGCC 1099 AGGCGGCGTCCT 1100 CGGGAAGCTTCAGAGTACCTTTGTATTTGAGGAAATAGGACGC
CAGAGTACCT CAATATCCTT ATTTCCTCAAAT CGCCTAAAGGATATTGGGCCTGAGGT
T
HSD3B2 NM_000198 1101 GCCTTCCTTT 1102 GGAGTAAATT 1103 ACTTCCAGCAGG 1104 GCCTTCCTTTAACCCTGATGTACTGGATTGGCTTCCTGCTGGA
AACCCTGATG GGGCTGAGTA AAGCCAATCCAG AGTAGTGAGCTTCCTACTCAGCCCAATTTACTCC
GG
HSP90AB1 NM_007355 1105 GCATTGTGAC 1106 GAAGTGCCTG 1107 ATCCGCTCCATA 1108 GCATTGTGACCAGCACCTACGGCTGGACAGCCAATATGGAGC
CAGCACCTAC GGCTTTCAT TTGGCTGTCCAG GGATCATGAAAGCCCAGGCACTTC
HSPA5 NM_005347 1109 GGCTAGTAGA 1110 GGTCTGCCCA 1111 TAATTAGACCTA 1112 GGCTAGTAGAACTGGATCCCAACACCAAACTCTTAATTAGACC
ACTGGATCCC AATGCTTTTC GGCCTCAGCTGC TAGGCCTCAGCTGCACTGCCCGAAAAGCATTTGGGCAGACC
AACA ACTGCC
HSPA8 NM_006597 1113 CCTCCCTCTG 1114 GCTACATCTA 1115 CTCAGGGCCCAC 1116 CCTCCCTCTGGTGGTGCTTCCTCAGGGCCCACCATTGAAGAG
GTGGTGCTT CACTTGGTTG CATTGAAGAGGT GTTGATTAAGCCAACCAAGTGTAGATGTAGC
GCTTAA TG
HSPB1 NM_001540 1117 CCGACTGGAG 1118 ATGCTGGCTG 1119 CGCACTTTTCTG 1120 CCGACTGGAGGAGCATAAAAGCGCAGCCGAGCCCAGCGCCC
GAGCATAAA ACTCTGCTC AGCAGACGTCCA CGCACTTTTCTGAGCAGACGTCCAGAGCAGAGTCAGCCAGCA
T
HSPB2 NM_001541 1121 CACCACTCCA 1122 TGGGACCAAA 1123 CACCTTTCCCTT 1124 CACCACTCCAGAGGTAGCAGCATCCTTGGGGGAAGGGAAAGG
GAGGTAGCAG CCATACATTG CCCCCAAGGAT TGCATGGTCCACAATGTATGGTTTGGTCCCA
HSPE1 NM_002157 1125 GCAAGCAACA 1126 CCAACTTTCA 1127 TCTCCACCCTTT 1128 GCAAGCAACAGTAGTCGCTGTTGGATCGGGTTCTAAAGGAAA
GTAGTCGCTG CGCTAACTGG CCTTTAGAACCC GGGTGGAGAGATTCAACCAGTTAGCGTGAAAGTTGG
T G
HSPG2 NM_005529 1129 GAGTACGTGT 1130 CTCAATGGTG 1131 CAGCTCCGTGCC 1132 GAGTACGTGTGCCGAGTGTTGGGCAGCTCCGTGCCTCTAGAG
GCCGAGTGTT ACCAGGACA TCTAGAGGCCT GCCTCTGTCCTGGTCACCATTGAG
ICAM1 NM_000201 1133 GCAGACAGTG 1134 CTTCTGAGAC 1135 CCGGCGCCCAAC 1136 GCAGACAGTGACCATCTACAGCTTTCCGGCGCCCAACGTGATT
ACCATCTACA CTCTGGCTTC GTGATTCT CTGACGAAGCCAGAGGTCTCAGAAG
GCTT GT
IER3 NM_003897 1137 GTACCTGGTG 1138 GCGTCTCCGC 1139 TCAAGTTGCCTC 1140 GTACCTGGTGCGCGAGAGCGTATCCCCAACTGGGACTTCCGA
CGCGAGAG TGTAGTGTT GGAAGTCCCAGT GGCAACTTGAACTCAGAACACTACAGCGGAGACGC
IFI30 NM_006332 1141 ATCCCATGAA 1142 GCACCATTCT 1143 AAAATTCCACCC 1144 ATCCCATGAAGCCCAGATACACAAAATTCCACCCCATGATCAA
GCCCAGATAC TAGTGGAGCA CATGATCAAGAA GAATCCTGCTCCACTAAGAATGGTGC
TCC
IFIT1 NM_001548 1145 TGACAACCAA 1146 CAGTCTGCCC 1147 AAGTTGCCCCAG 1148 TGACAACCAAGCAAATGTGAGGAGTCTGGTGACCTGGGGCAA
GCAAATGTGA ATGTGGTAAT GTCACCAGACTC CTTTGCCTGGATGTATTACCACATGGGCAGACTG
IFNG NM_000619 1149 GCTAAAACAG 1150 CAACCATTAC 1151 TCGACCTCGAAA 1152 GCTAAAACAGGGAAGCGAAAAAGGAGTCAGATGCTGTTTCGA
GGAAGCGAAA TGGGATGCTC CAGCATCTGACT GGTCGAAGAGCATCCCAGTAATGGTTG
CC
IGF1 NM_000618 1153 TCCGGAGCTG 1154 CGGACAGAGC 1155 TGTATTGCGCAC 1156 TCCGGAGCTGTGATCTAAGGAGGCTGGAGATGTATTGCGCAC
TGATCTAAGG GAGCTGACTT CCCTCAAGCCTG CCCTCAAGCCTGCCAAGTCAGCTCGCTCTGTCCG
A
IGF1R NM_000875 1157 GCATGGTAGC 1158 TTTCCGGTAA 1159 CGCGTCATACCA 1160 GCATGGTAGCCGAAGATTTCACAGTCAAAATCGGAGATTTTGG
CGAAGATTTC TAGTCTGTCT AAATCTCCGATT TATGACGCGAGATATCTATGAGACAGACTATTACCGGAAA
A CATAGATATC TTGA
IGF2 NM_000612 1161 CCGTGCTTCC 1162 TGGACTGCTT 1163 TACCCCGTGGGC 1164 CCGTGCTTCCGGACAACTTCCCCAGATACCCCGTGGGCAAGT
GGACAACTT CCAGGTGTCA AAGTTCTTCCAA TCTTCCAATATGACACCTGGAAGCAGTCCA
IGFBP2 NM_000597 1165 GTGGACAGCA 1166 CCTTCATACC 1167 CTTCCGGCCAGC 1168 GTGGACAGCACCATGAACATGTTGGGCGGGGGAGGCAGTGCT
CCATGAACA CGACTTGAGG ACTGCCTC GGCCGGAAGCCCCTCAAGTCGGGTATGAAGG
IGFBP3 NM_000598 1169 ACATCCCAAC 1170 CCACGCCCTT 1171 ACACCACAGAAG 1172 ACATCCCAACGCATGCTCCTGGAGCTCACAGCCTTCTGTGGTG
GCATGCTC GTTTCAGA GCTGTGAGCTCC TCATTTCTGAAACAAGGGCGTGG
IGFBP5 NM_000599 1173 TGGACAAGTA 1174 CGAAGGTGTG 1175 CCCGTCAACGTA 1176 TGGACAAGTACGGGATGAAGCTGCCAGGCATGGAGTACGTTG
CGGGATGAAG GCACTGAAAG CTCCATGCCTGG ACGGGGACTTTCAGTGCCACACCTTCG
CT T
IGFBP6 NM_002178 1177 TGAACCGCAG 1178 GTCTTGGACA 1179 ATCCAGGCACCT 1180 TGAACCGCAGAGACCAACAGAGGAATCCAGGCACCTCTACCA
AGACCAACAG CCCGCAGAAT CTACCACGCCCT CGCCCTCCCAGCCCAATTCTGCGGGTGTCCAAGAC
C
IL10 NM_000572 1181 CTGACCACGC 1182 CCAAGCCCAG 1183 TTGAGCTGTTTT 1184 CTGACCACGCTTTCTAGCTGTTGAGCTGTTTTCCCTGACCTCC
TTTCTAGCTG AGACAAGATA CCCTGACCTCCC CTCTAATTTATCTTGTCTCTGGGCTTGG
A
IL11 NM_000641 1185 TGGAAGGTTC 1186 TCTTGACCTT 1187 CCTGTGATCAAC 1188 TGGAAGGTTCCACAAGTCACCCTGTGATCAACAGTACCCGTAT
CACAAGTCAC GCAGCTTTGT AGTACCCGTATG GGGACAAAGCTGCAAGGTCAAGA
GG
IL17A NM_002190 1189 TCAAGCAACA 1190 CAGCTCCTTT 1191 TGGCTTCTGTCT 1192 TCAAGCAACACTCCTAGGGCCTGGCTTCTGTCTGATCAAGGCA
CTCCTAGGGC CTGGGTTGTG GATCAAGGCACC CCACACAACCCAGAAAGGAGCTG
IL1A NM_000575 1193 GGTCCTTGGT 1194 GGATGGAGCT 1195 TCTCCACCCTGG 1196 GGTCCTTGGTAGAGGGCTACTTTACTGTAACAGGGCCAGGGT
AGAGGGCTAC TCAGGAGAGA CCCTGTTACAGT GGAGAGTTCTCTCCTGAAGCTCCATCC
TT
IL1B NM_000576 1197 AGCTGAGGAA 1198 GGAAAGAAGG 1199 TGCCCACAGACC 1200 AGCTGAGGAAGATGCTGGTTCCCTGCCCACAGACCTTCCAGG
GATGCTGGTT TGCTCAGGTC TTCCAGGAGAAT AGAATGACCTGAGCACCTTCTTTCC
IL2 NM_000586 1201 ACCTCAACTC 1202 CACTGTTTGT 1203 TGCAACTCCTGT 1204 ACCTCAACTCCTGCCACAATGTACAGGATGCAACTCCTGTCTT
CTGCCACAAT GACAAGTGCA CTTGCATTGCAC GCATTGCACTAAGTCTTGCACTTGTCACAAACAGTG
AG
IL6 NM_000600 1205 CCTGAACCTT 1206 ACCAGGCAAG 1207 CCAGATTGGAAG 1208 CCTGAACCTTCCAAAGATGGCTGAAAAAGATGGATGCTTCCAA
CCAAAGATGG TCTCCTCATT CATCCATCTTTT TCTGGATTCAATGAGGAGACTTGCCTGGT
TCA
IL6R NM_000565 1209 CCAGCTTATC 1210 CTGGCGTAGA 1211 CCTTTGGCTTCA 1212 CCAGCTTATCTCAGGGGTGTGCGGCCTTTGGCTTCACGGAAG
TCAGGGGTGT ACCTTCCG CGGAAGAGCCTT AGCCTTGCGGAAGGTTCTACGCCAG
IL6ST NM_002184 1213 GGCCTAATGT 1214 AAAATTGTGC 1215 CATATTGCCCAG 1216 GGCCTAATGTTCCAGATCCTTCAAAGAGTCATATTGCCCAGTG
TCCAGATCCT CTTGGAGGAG TGGTCACCTCAC GTCACCTCACACTCCTCCAAGGCACAATTTT
A
IL8 NM_000584 1217 AAGGAACCAT 1218 ATCAGGAAGG 1219 TGACTTCCAAGC 1220 AAGGAACCATCTCACTGTGTGTAAACATGACTTCCAAGCTGGC
CTCACTGTGT CTGCCAAGAG TGGCCGTGGC CGTGGCTCTCTTGGCAGCCTTCCTGAT
GTAAAC
ILF3 NM_004516 1221 GACACGCCAA 1222 CTCAAGACCC 1223 ACACAAGACTTC 1224 GACACGCCAAGTGGTTCCAGGCCAGAGCCAACGGGCTGAAGT
GTGGTTCC GGATCACAA AGCCCGTTGGCT CTTGTGTCATTGTGATCCGGGTCTTGAG
ILK NM_ 1225 CTCAGGATTT 1226 AGGAGCAGGT 1227 ATGTGCTCCCAG 1228 CTCAGGATTTTCTCGCATCCAAATGTGCTCCCAGTGCTAGGTG
001014794 TCTCGCATCC GGAGACTGG TGCTAGGTGCCT CCTGCCAGTCTCCACCTGCTCCT
IMMT NM_006839 1229 CTGCCTATGC 1230 GCTTTTCTGG 1231 CAACTGCATGGC 1232 CTGCCTATGCCAGACTCAGAGGAATCGAACAGGCTGTTCAGA
CAGACTCAGA CTTCCTCTTC TCTGAACAGCCT GCCATGCAGTTGCTGAAGAGGAAGCCAGAAAAGC
ING5 NM_032329 1233 CCTACAGCAA 1234 CATCTCGTAG 1235 CCAGCTGCACTT 1236 CCTACAGCAAGTGCAAGGAATACAGTGACGACAAAGTGCAGC
GTGCAAGGAA GTCTGCATGG TGTCGTCACTGT TGGCCATGCAGACCTACGAGATG
INHBA NM_002192 1237 GTGCCCGAGC 1238 CGGTAGTGGT 1239 ACGTCCGGGTCC 1240 GTGCCCGAGCCATATAGCAGGCACGTCCGGGTCCTCACTGTC
CATATAGCA TGATGACTGT TCACTGTCCTTC CTTCCACTCAACAGTCATCAACCACTACCG
TGA C
INSL4 NM_002195 1241 CTGTCATATT 1242 CAGATTCCAG 1243 TGAGAAGACATT 1244 CTGTCATATTGCCCCATGCCTGAGAAGACATTCACCACCACCC
GCCCCATGC CAGCCACC CACCACCACCCC CAGGAGGGTGGCTGCTGGAATCTG
ITGA1 NM_181501 1245 GCTTCTTCTG 1246 CCTGTAGATA 1247 TTGCTGGACAGC 1248 GCTTCTTCTGGAGATGTGCTCTATATTGCTGGACAGCCTCGGT
GAGATGTGCT ATGACCTGGC CTCGGTACAATC ACAATCATACAGGCCAGGTCATTATCTACAGG
CT CT
ITGA3 NM_002204 1249 CCATGATCCT 1250 GAAGCTTTGT 1251 CACTCCAGACCT 1252 CCATGATCCTCACTCTGCTGGTGGACTATACACTCCAGACCTC
CACTCTGCTG AGCCGGTGAT CGCTTAGCATGG GCTTAGCATGGTAAATCACCGGCTACAAAGCTTC
ITGA4 NM_000885 1253 CAACGCTTCA 1254 GTCTGGCCGG 1255 CGATCCTGCATC 1256 CAACGCTTCAGTGATCAATCCCGGGGCGATTTACAGATGCAG
GTGATCAATC GATTCTTT TGTAAATCGCCC GATCGGAAAGAATCCCGGCCAGAC
C
ITGA5 NM_002205 1257 AGGCCAGCCC 1258 GTCTTCTCCA 1259 TCTGAGCCTTGT 1260 AGGCCAGCCCTACATTATCAGAGCAAGAGCCGGATAGAGGAC
TACATTATCA CAGTCCAGCA CCTCTATCCGGC AAGGCTCAGATCTTGCTGGACTGTGGAGAAGAC
ITGA6 NM_000210 1261 CAGTGACAAA 1262 GTTTAGCCTC 1263 TCGCCATCTTTT 1264 CAGTGACAAACAGCCCTTCCAACCCAAGGAATCCCACAAAAGA
CAGCCCTTCC ATGGGCGTC GTGGGATTCCTT TGGCGATGACGCCCATGAGGCTAAAC
ITGA7 NM_002206 1265 GATATGATTG 1266 AGAACTTCCA 1267 CAGCCAGGACCT 1268 GATATGATTGGTCGCTGCTTTGTGCTCAGCCAGGACCTGGCCA
GTCGCTGCTT TTCCCCACCA GGCCATCCG TCCGGGATGAGTTGGATGGTGGGGAATGGAAGTTCT
TG T
ITGAD NM_005353 1269 GAGCCTGGTG 1270 ACTGTCAGGA 1271 CAACTGAAAGGC 1272 GAGCCTGGTGGATCCCATCGTCCAACTGAAAGGCCTGACGTT
GATCCCAT TGCCCGTG CTGACGTTCACG CACGGCCACGGGCATCCTGACAGT
ITGB3 NM_000212 1273 ACCGGGAGCC 1274 CCTTAAGCTC 1275 AAATACCTGCAA 1276 ACCGGGGAGCCCTACATGACGAAAATACCTGCAACCGTTACT
CTACATGAC TTTCACTGAC CCGTTACTGCCG GCCGTGACGAGATTGAGTCAGTGAAAGAGCTTAAGG
TCAATCT TGAC
ITGB4 NM_000213 1277 CAAGGTGCCC 1278 GCGCACACCT 1279 CACCAACCTGTA 1280 CAAGGTGCCCTCAGTGGAGCTCACCAACCTGTACCCGTATTG
TCAGTGGA TCATCTCAT CCCGTATTGCGA CGACTATGAGATGAAGGTGTGCGC
ITGB5 NM_002213 1281 TCGTGAAAGA 1282 GGTGAACATC 1283 TGCTATGTTTCT 1284 TCGTGAAAGATGACCAGGAGGCTGTGCTATGTTTCTACAAAAC
TGACCAGGAG ATGACGCAGT ACAAAACCGCCA CGCCAAGGACTGCGTCATGATGTTCACC
AGG
ITPR1 NM_002222 1285 GAGGAGGTGT 1286 GTAATCCCAT 1287 CCATCCTAACGG 1288 GAGGAGGTGTGGGTGTTCCGCTTCCATCCTAACGGAACGAGC
GGGTGTTCC GTCCGCGA AACGAGCTCCCT TCCCTCTTCGCGGACATGGGATTAC
ITPR3 NM_002224 1289 TTGCCATCGT 1290 ATGGAGCTGG 1291 TCCAGGTCTCGG 1292 TTGCCATCGTGTCAGTGCCCGTGTCTGAGATCCGAGACCTGG
GTCAGTGC CGTCATTG ATCTCAGACACG ACTTTGCCAATGACGCCAGCTCCAT
ITSN1 NM_003024 1293 TAACTGGGAT 1294 CTCTGCCTTA 1295 AGCCCTCTCTCA 1296 TAACTGGGATGCATGGGCAGCCCAGCCCTCTCTCACCGTTCC
GCATGGGC ACTGGCCG CCGTTCCAAGTG AAGTGCCGGCCAGTTAAGGCAGAG
JAG1 NM_000214 1297 TGGCTTACAC 1298 GCATAGCTGT 1299 ACTCGATTTCCC 1300 TGGCTTACACTGGCAATGGTAGTTTCTGTGGTTGGCTGGGAAA
TGGCAATGG GAGATGCGG AGCCAACCACAG TCGAGTGCCGCATCTCACAGCTATGC
JUN NM_002228 1301 GACTGCAAAG 1302 TAGCCATAAG 1303 CTATGACGATGC 1304 GACTGCAAAGATGGAAACGACCTTCTATGACGATGCCCTCAAC
ATGGAAACGA GTCCGCTCTC CCTCAACGCCTC GCCTCGTTCCTCCCGTCCGAGAGCGGACCTTATGGCTA
JUNB NM_002229 1305 CTGTCAGCTG 1306 AGGGGGTGTC 1307 CAAGGGACACGC 1308 CTGTCAGCTGCTGCTTGGGGTCAAGGGACACGCCTTCTGAAC
CTGCTTGG CGTAAAGG CTTCTGAACGT GTCCCCTGCCCCTTTACGGACACCCCCT
KCNN2 NM_021614 1309 TGTGCTATTC 1310 GGGCATAGGA 1311 TTATACATTCAC 1312 TGTGCTATTCATCCCATACCTGGGAATTATACATTCACATGGA
ATCCCATACC GAAGGCAAG ATGGACGGCCCG CGGCCCGGCTTGCCTTCTCCTATGCCC
TG
KCTD12 NM_138444 1313 AGCAGTTACT 1314 TGGAGACCTG 1315 ACTCTTAGGCGG 1316 AGCAGTTACTGGCAAGAGGGAGAAAGGACGCTGCCGCCTAAG
GGCAAGAGGG AGCAGCCT CAGCGTCCTTTC AGTGCAAGGCTGCTCAGGTCTCCA
KHDRBS3 NM_006558 1317 CGGGCAAGAA 1318 CTGTAGACGC 1319 CAAGACACAAGG 1320 CGGGCAAGAAGAGTGGACTAACTCAAGACACAAGGCACCTTC
GAGTGGAC CCTTTGCTGT CACCTTCAGCGA AGCGAGGACAGCAAAGGGCGTCTACAG
KIAA0196 NM_014846 1321 CAGACACCAG 1322 AACATTGTGA 1323 TCCCCAGTGTCC 1324 CAGACACCAGCTCTGAGGCCAGTTAATCATCCCCAGTGTCCAG
CTCTGAGGC GGCGGACC AGGCACAGAGTA GCACAGAGTAGTCGGTCCGCCTCACAATGTT
KIAA0247 NM_014734 1325 CCGTGGGACA 1326 GAAGCAAGTC 1327 TCCGCTAGTGAT 1328 CCGTGGGACATGGAGTGTTCCTTCCGCTAGTGATCCTTTGCAC
TGGAGTGT CGTCTCCAAG CCTTTGCACCCT CCTGCTTGGAGACGGACTTGCTTC
KIF4A NM_012310 1329 AGAGCTGGTC 1330 GCTGGTCTTG 1331 CAGGTCAGCAAA 1332 AGAGCTGGTCTCCTCCAAAATACAGGTCAGCAAACTTGAAAGC
TCCTCCAAAA CTCTGTTTCA CTTGAAAGCAGC AGCCTGAAACAGAGCAAGACCAGC
C
KIT NM_000222 1333 GAGGCAACTG 1334 GGCACTCGGC 1335 TTACAGCGACAG 1336 GAGGCAACTGCTTATGGCTTAATTAAGTCAGATGCGGCCATGA
CTTATGGCTT TTGAGCAT TCATGGCCGCAT CTGTCGCTGTAAAGATGCTCAAGCCGAGTGCC
AATTA
KLC1 NM_182923 1337 AGTGGCTACG 1338 TGAGCCACAG 1339 CAACACGCAGCA 1340 AGTGGCTACGGGATGAACTGGCCAACACGCAGCAGAAACTGC
GGATGAACTG ACTGCTCACT GAAACTGCAGAA AGAAGAGTGAGCAGTCTGTGGCTCA
KLF6 NM_001300 1341 CACGAGACCG 1342 GCTCTAGGCA 1343 AGTACTCCTCCA 1344 CACGAGACCGGCTACTTCTCGGCGCTGCCGTCTCTGGAGGAG
GCTACTTCTC GGTCTGTTGC GAGACGGCAGCG TACTGGCAACAGACCTGCCTAGAGC
KLK1 NM_002257 1345 AACACAGCCC 1346 CCAGGAGGCT 1347 TCAGTGAGAGCT 1348 AACACAGCCCAGTTTGTTCATGTCAGTGAGAGCTTCCCACACC
AGTTTGTTCA CATGTTGAAG TCCCACACCCTG CTGGCTTCAACATGAGCCTCCTGG
KLK10 NM_002776 1349 GCCCAGAGGC 1350 CAGAGGTTTG 1351 CCTCTTCCTCCC 1352 GCCCAGAGGCTCCATCGTCCATCCTCTTCCTCCCCAGTCGGCT
TCCATCGT AACAGTGCAG CAGTCGGCTGA GAACTCTCCCCTTGTCTGCACTGTTCAAACCTCTG
ACA
KLK11 NM_006853 1353 CACCCCGGCT 1354 CATCTTCACC 1355 CCTCCCCAACAA 1356 CACCCCGGCTTCAACAACAGCCTCCCCAACAAAGACCACCGC
TCAACAAC AGCATGATGT AGACCACCGCA AATGACATCATGCTGGTGAAGATG
CA
KLK14 NM_022046 1357 CCCCTAAAAT 1358 CTCATCCTCT 1359 CAGCACTTCAAG 1360 CCCCTAAAATGTTCCTCCTGCTGACAGCACTTCAAGTCCTGGC
GTTCCTCCTG TGGCTCTGTG TCCTGGCTATAG TATAGCCATGACACAGAGCCAAGAGGATGAG
CCA
KLK2 NM_005551 1361 AGTCTCGGAT 1362 TGTACACAGC 1363 TTGGGAATGCTT 1364 AGTCTCGGATTGTGGGAGGCTGGGAGTGTGAGAAGCATTCCC
TGTGGGAGG CACCTGCC CTCACACTCCCA AACCCTGGCAGGTGGCTGTGTACA
KLK3 NM_001648 1365 CCAAGCTTAC 1366 AGGGTGAGGA 1367 ACCCACATGGTG 1368 CCAAGCTTACCACCTGCACCCGGAGAGCTGTGTCACCATGTG
CACCTGCAC AGACAACCG ACACAGCTCTCC GGTCCCGGTTGTCTTCCTCACCCT
KLRK1 NM_007360 1369 TGAGAGCCAG 1370 ATCCTGGTCC 1371 TGTCTCAAAATG 1372 TGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGCCTTCTG
GCTTCTTGTA TCTTTGCTGT CCAGCCTTCTGA AAAGTATACAGCAAAGAGGACCAGGAT
A
KPNA2 NM_002266 1373 TGATGGTCCA 1374 AAGCTTCACA 1375 ACTCCTGTTTTC 1376 TGATGGTCCAAATGAACGAATTGGCATGGTGGTGAAAACAGGA
AATGAACGAA AGTTGGGGC ACCACCATGCCA GTTGTGCCCCAACTTGTGAAGCTT
KRT1 NM_006121 1377 TGGACAACAA 1378 TATCCTCGTA 1379 CCTCAGCAATGA 1380 TGGACAACAACCGCAGTCTCGACCTGGACAGCATCATTGCTGA
CCGCAGTC CTGGGCCTTG TGCTGTCCAGGT GGTCAAGGCCCAGTACGAGGATA
KRT15 NM_002275 1381 GCCTGGTTCT 1382 CTTGCTGGTC 1383 TGAACAAAGAGG 1384 GCCTGGTTCTTCAGCAAGACTGAGGAGCTGAACAAAGAGGTG
TCAGCAAGAC TGGATCATTT TGGCCTCCAACA GCCTCCAACACAGAAATGATCCAGACCAGCAAG
C
KRT18 NM_000224 1385 AGAGATCGAG 1386 GGCCTTTTAC 1387 TGGTTCTTCTTC 1388 AGAGATCGAGGCTCTCAAGGAGGAGCTGCTCTTCATGAAGAA
GCTCTCAAGG TTCCTCTTCG ATGAAGAGCAGC GAACCACGAAGAGGAAGTAAAAGGCC
TCC
KRT2 NM_000423 1389 CCAGTGACGC 1390 GGGCATGGCT 1391 ACCTAGACAGCA 1392 CCAGTGACGCCTCTGTGTTCTGGGGCGGAATCTGTGCTGTCTA
CTCTGTGTT AGAAGCAC CAGATTCCGCCC GGTTTGTGCTTCTAGCCATGCCC
KRT5 NM_000424 1393 TCAGTGGAGA 1394 TGCCATATCC 1395 CCAGTCAACATC 1396 TCAGTGGAGAAGGAGTTGGACCAGTCAACATCTCTGTTGTCAC
AGGAGTTGGA AGAGGAAACA TCTGTTGTCACA AAGCAGTGTTTCCTCTGGATATGGCA
AGCA
KRT75 NM_004693 1397 TCAAAGTCAG 1398 ACGTCCTTTT 1399 TTCATTCTCAGC 1400 TCAAAGTCAGGTACGAAGATGAAATTAACAAGCGCACAGCTGC
GTACGAAGAT TCAGGGCTAC AGCTGTGCGCTT TGAGAATGAATTTGTAGCCCTGAAAAAGGACGT
GAAATT AA GT
KRT76 NM_015848 1401 ATCTCCAGAC 1402 TCAGGGAATT 1403 TCTGGGCTTCAG 1404 ATCTCCAGACTGCTGGTTCCCAGGGAACCCTCCCTACATCTGG
TGCTGGTTCC AGGGGACAGA ATCCTGACTCCC GCTTCAGATCCTGACTCCCTTCTGTCCCCTAATTCCCTGA
KRT8 NM_002273 1405 GGATGAAGCT 1406 CATATAGCTG 1407 CGTCGGTCAGCC 1408 GGATGAAGCTTACATGAACAAGGTAGAGCTGGAGTCTCGCCT
TACATGAACA CCTGAGGAAG CTTCCAGGC GGAAGGGCTGACCGACGAGATCAACTTCCTCAGGCAGCTATA
AGGTAGA TTGAT TG
L1CAM NM_000425 1409 CTTGCTGGCC 1410 TGATTGTCCG 1411 ATCTACGTTGTC 1412 CTTGCTGGCCAATGCCTACATCTACGTTGTCCAGCTGCCAGCC
AATGCCTA CAGTCAGG CAGCTGCCAGCC AAGATCCTGACTGCGGACAATCA
LAG3 NM_002286 1413 GCCTTAGAGC 1414 CGGTTCTTGC 1415 TCTATCTTGCTC 1416 GCCTTAGAGCAAGGGATTCACCCTCCGCAGGCTCAGAGCAAG
AAGGGATTCA TCCAGCTC TGAGCCTGCGGA ATAGAGGAGCTGGAGCAAGAACCG
LAMA3 NM_000227 1417 CCTGTCACTG 1418 TGGGTTACTG 1419 ATTCAGACTGAC 1420 CCTGTCACTGAAGCCTTGGAAGTCCAGGGGCCTGTCAGTCTG
AAGCCTTGG GTCAGGACAA AGGCCCCTGGAC AATGGTTGTCCTGACCAGTAACCCA
C
LAMA4 NM_002290 1421 GATGCACTGC 1422 CAGAGGATAC 1423 CTCTCCATCGAG 1424 GATGCACTGCGGTTAGCAGCGCTCTCCATCGAGGAAGGCAAA
GGTTAGCAG GCTCAGCACC GAAGGCAAATCC TCCGGGGTGCTGAGCGTATCCTCTG
LAMA5 NM_005560 1425 CTCCTGGCCA 1426 ACACAAGGCC 1427 CTGTTCCTGGAG 1428 CTCCTGGCCAACAGCACTGCACTAGAAGAGGCCATGCTCCAG
ACAGCACT CAGCCTCT CATGGCCTCTTC GAACAGCAGAGGCTGGGCCTTGTGT
LAMB1 NM_002291 1429 CAAGGAGACT 1430 CGGCAGAACT 1431 CAAGTGCCTGTA 1432 CAAGGAGACTGGGAGGTGTCTCAAGTGCCTGTACCACACGGA
GGGAGGTGTC GACAGTGTTC CCACACGGAAGG AGGGGAACACTGTCAGTTCTGCCG
LAMB3 NM_000228 1433 ACTGACCAAG 1434 GTCACACTTG 1435 CCACTCGCCATA 1436 ACTGACCAAGCCTGAGACCTACTGCACCCAGTATGGCGAGTG
CCTGAGACCT CAGCATTTCA CTGGGTGCAGT GCAGATGAAATGCTGCAAGTGTGAC
LAMC1 NM_002293 1437 GCCGTGATCT 1438 ACCTGCTTGC 1439 CCTCGGTACTTC 1440 GCCGTGATCTCAGACAGCTACTTTCCTCGGTACTTCATTGCTC
CAGACAGCTA CCAAGAACT ATTGCTCCTGCA CTGCAAAGTTCTTGGGCAAGCAGGT
C
LAMC2 NM_005562 1441 ACTCAAGCGG 1442 ACTCCCTGAA 1443 AGGTCTTATCAG 1444 ACTCAAGCGGAAATTGAAGCAGATAGGTCTTATCAGCACAGTC
AAATTGAAGC GCCGAGACAC CACAGTCTCCGC TCCGCCTCCTGGATTCAGTGTCTCGGCTTCAGGGAGT
A T CTCC
LAPTM5 NM_006762 1445 TGCTGGACTT 1446 TGAGATAGGT 1447 TCCTGACCCTCT 1448 TGCTGGACTTCTGCCTGAGCATCCTGACCCTCTGCAGCTCCTA
CTGCCTGAG GGGCACTTCC GCAGCTCCTACA CATGGAAGTGCCCACCTATCTCA
LGALS3 NM_002306 1449 AGCGGAAAAT 1450 CTTGAGGGTT 1451 ACCCAGATAACG 1452 AGCGGAAAATGGCAGACAATTTTTCGCTCCATGATGCGTTATC
GGCAGACAAT TGGGTTTCCA CATCATGGAGCG TGGGTCTGGAAACCCAAACCCTCAAG
A
LIG3 NM_002311 1453 GGAGGTGGAG 1454 ACAGGTGTCA 1455 CTGGACGCTCAG 1456 GGAGGTGGAGAAGGAGCCGGGCCAGAGACGAGCTCTGAGCG
AAGGAGCC TCAGCGAGG AGCTCGTCTCTG TCCAGGCCTCGCTGATGACACCTGT
LIMS1 NM_004987 1457 TGAACAGTAA 1458 TTCTGGGAAC 1459 ACTGAGCGCACA 1460 TGAACAGTAATGGGGAGCTGTACCATGAGCAGTGTTTCGTGTG
TGGGGAGCTG TGCTGGAAG CGAAACACTGCT CGCTCAGTGCTTCCAGCAGTTCCCAGAA
LOX NM_002317 1461 CCAATGGGAG 1462 CGCTGAGGCT 1463 CAGGCTCAGCAA 1464 CCAATGGGAGAACAACGGGCAGGTGTTCAGCTTGCTGAGCCT
AACAACGG GGTACTGTG GCTGAACACCTG GGGCTCACAGTACCAGCCTCAGCG
LRP1 NM_002332 1465 TTTGGCCCAA 1466 GTCTCGATGC 1467 TCCCGGCTGGGC 1468 TTTGGCCCAATGGGCTAAGCCTGGACATCCCGGCTGGGCGCC
TGGGCTAAG GGTCGTAGAA GCCTCTACT TCTACTGGGTGGATGCCTTCTACGACCGCATCGAGAC
G
LTBP2 NM_000428 1469 GCACACCCAT 1470 GATGGCTGGC 1471 CTTTGCAGCCCT 1472 GCACACCCATCCTTGAGTCTCCTTTGCAGCCCTCAGAACTCCA
CCTTGAGTCT CACGTAGT CAGAACTCCAGC GCCCCACTACGTGGCCAGCCATC
LUM NM_002345 1473 GGCTCTTTTG 1474 AAAAGCAGCT 1475 CCTGACCTTCAT 1476 GGCTCTTTTGAAGGATTGGTAAACCTGACCTTCATCCATCTCC
AAGGATTGGT GAAACAGCAT CCATCTCCAGCA AGCACAATCGGCTGAAAGAGGATGCTGTTTCAGCTGCTTTT
AA C
MAGEA4 NM_002362 1477 GCATCTAACA 1478 CAGAGTGAAG 1479 CAGCTTCCCTTG 1480 GCATCTAACAGCCCTGTGCAGCAGCTTCCCTTGCCTCGTGTAA
GCCCTGTGC AATGGGCCTC CCTCGTGTAACA CATGAGGCCCATTCTTCACTCTG
MANF NM_006010 1481 CAGATGTGAA 1482 AAGGGAATCC 1483 TTCCTGATGATG 1484 CAGATGTGAAGCCTGGAGCTTTCCTGATGATGCTGGCCCTACA
GCCTGGAGC CCTCATGG CTGGCCCTACAG GTACCCCCATGAGGGGATTCCCTT
MAOA NM_000240 1485 GTGTCAGCCA 1486 CGACTACGTC 1487 CCGCGATACTCG 1488 GTGTCAGCCAAAGCATGGAGAATCAAGAGAAGGCGAGTATCG
AAGCATGGA GAACATGTGG CCTTCTCTTGAT CGGGCCACATGTTCGACGTAGTCG
MAP3K5 NM_005923 1489 AGGACCAAGA 1490 CCTGTGGCCA 1491 CAGCCCAGAGAC 1492 AGGACCAAGAGGCTACGGAAAAGCAGCAGACATCTGGTCTCT
GGCTACGGA TTTCAATGAT CAGATGTCTGCT GGGCTGTACAATCATTGAAATGGCCACAGG
MAP3K7 NM_145333 1493 CAGGCAAGAA 1494 CCTGTACCAG 1495 TGCTGGTCCTTT 1496 CAGGCAAGAACTAGTTGCAGAACTGGACCAGGATGAAAAGGA
CTAGTTGCAG GCGAGATGTA TCATCCTGGTCC CCAGCAAAATACATCTCGCCTGGTACAGG
AA T
MAP4K4 NM_004834 1497 TCGCCGAGAT 1498 CTGTTGTCTC 1499 AACGTTCCTTGT 1500 TCGCCGAGATTTCCTGAGACTGCAGCAGGAGAACAAGGAACG
TTCCTGAG CGAAGAGCCT TCTCCTGCTGCA TTCCGAGGCTCTTCGGAGACAACAG
MAP7 NM_003980 1501 GAGGAACAGA 1502 CTGCCAACTG 1503 CATGTACAACAA 1504 GAGGAACAGAGGTGTCTGCACTTCCATGTACAACAAACGCTCC
GGTGTCTGCA GCTTTCCA ACGCTCCGGGAA GGGAAATGGAAAGCCAGTTGGCAG
C
MAPKAPK3 NM_004635 1505 AAGCTGCAGA 1506 GTGGGCAATG 1507 ATTGGCACTGCC 1508 AAGCTGCAGAGATAATGCGGGATATTGGCACTGCCATCCAGTT
GATAATGCGG TTATGGCTG ATCCAGTTTCTG TCTGCACAGCCATAACATTGCCCAC
MCM2 NM_004526 1509 GACTTTTGCC 1510 GCCACTAACT 1511 ACAGCTCATTGT 1512 GACTTTTGCCCGCTACCTTTCATTCCGGCGTGACAACAATGAG
CGCTACCTTT GCTTCAGTAT TGTCACGCCGGA CTGTTGCTCTTCATACTGAAGCAGTTAGTGGC
C GAAGAG
MCM3 NM_002388 1513 GGAGAACAAT 1514 ATCTCCTGGA 1515 TGGCCTTTCTGT 1516 GGAGAACAATCCCCTTGAGACAGAATATGGCCTTTCTGTCTAC
CCCCTTGAGA TGGTGATGGT CTACAAGGATCA AAGGATCACCAGACCATCACCATCCAGGAGAT
CCA
MCM6 NM_005915 1517 TGATGGTCCT 1518 TGGGACAGGA 1519 CAGGTTTCATAC 1520 TGATGGTCCTATGTGTCACATTCATCACAGGTTTCATACCAAC
ATGTGTCACA AACACACCAA CAACACAGGCTT ACAGGCTTCAGCACTTCCTTTGGTGTGTTTCCTGTCCCA
TTCA CAGCAC
MDK NM_002391 1521 GGAGCCGACT 1522 GACTTTGGTG 1523 ATCACACGCACC 1524 GGAGCCGACTGCAAGTACAAGTTTGAGAACTGGGGTGCGTGT
GCAAGTACA CCTGTGCC CCAGTTCTCAAA GATGGGGGCACAGGCACCAAAGTC
MDM2 NM_002392 1525 CTACAGGGAC 1526 ATCCAACCAA 1527 CTTACACCAGCA 1528 CTACAGGGACGCCATCGAATCCGGATCTTGATGCTGGTGTAAG
GCCATCGAA TCACCTGAAT TCAAGATCCGG TGAACATTCAGGTGATTGGTTGGAT
GTT
MELK NM_014791 1529 AGGATCGCCT 1530 TGCACATAAG 1531 CCCGGGTTGTCT 1532 AGGATCGCCTGTCAGAAGAGGAGACCCGGGTTGTCTTCCGTC
GTCAGAAGAG CAACAGCAGA TCCGTCAGATAG AGATAGTATCTGCTGTTGCTTATGTGCA
MET NM_000245 1533 GACATTTCCA 1534 CTCCGATCGC 1535 TGCCTCTCTGCC 1536 GACATTTCCAGTCCTGCAGTCAATGCCTCTCTGCCCCACCCTT
GTCCTGCAGT ACACATTTGT CCACCCTTTGT TGTTCAGTGTGGCTGGTGCCACGACAAATGTGTGCGATCGGA
CA G
MGMT NM_002412 1537 GTGAAATGAA 1538 GACCCTGCTC 1539 CAGCCCTTTGGG 1540 GTGAAATGAAACGCACCACACTGGACAGCCCTTTGGGGAAGC
ACGCACCACA ACAACCAGAC GAAGCTGG TGGAGCTGTCTGGTTGTGAGCAGGGTC
MGST1 NM_020300 1541 ACGGATCTAC 1542 TCCATATCCA 1543 TTTGACACCCCT 1544 ACGGATCTACCACACCATTGCATATTTGACACCCCTTCCCCAG
CACACCATTG ACAAAAAAAC TCCCCAGCCA CCAAATAGAGCTTTGAGTTTTTTTGTTGGATATGGA
C TCAAAG
MICA NM_000247 1545 ATGGTGAATG 1546 AAGCCAGAAG 1547 CGAGGCCTCAGA 1548 ATGGTGAATGTCACCCGCAGCGAGGCCTCAGAGGGCAACATT
TCACCCGC CCCTGCAT GGGCAACATTAC ACCGTGACATGCAGGGCTTCTGGCTT
MKI67 NM_002417 1549 GATTGCACCA 1550 TCCAAAGTGC 1551 CCACTCTTCCTT 1552 GATTGCACCAGGGCAGAACAGGGGAGGGTGTTCAAGGAAGAG
GGGCAGAA CTCTGCTAAG GAACACCCTCCC TGGCTCTTAGCAGAGGCACTTTGGA
A
MLXIP NM_014938 1553 TGCTTAGCTG 1554 CAGCCTACTC 1555 CATGAGATGCCA 1556 TGCTTAGCTGGCATGTGGCCGCATGAGATGCCAGGAGACCCT
GCATGTGG TCCATGGGC GGAGACCCTTCC TCCCTGCCCATGGAGAGTAGGCTG
MMP11 NM_005940 1557 CCTGGAGGCT 1558 TACAATGGCT 1559 ATCCTCCTGAAG 1560 CCTGGAGGCTGCAACATACCTCAATCCTGTCCCAGGCCGGAT
GCAACATACC TTGGAGGATA CCCTTTTCGCAG CCTCCTGAAGCCCTTTTCGCAGCACTGCTATCCTCCAAAGCCA
GCA C TTGTA
MMP2 NM_004530 1561 CAGCCAGAAG 1562 AGACACCATC 1563 AAGTCCGAATCT 1564 CAGCCAGAAGCGGAAACTTAAAAAGTCCGAATCTCTGCTCCCT
CGGAAACTTA ACCTGTGCC CTGCTCCCTGCA GCAGGGCACAGGTGATGGTGTCT
MMP7 NM_002423 1565 GGATGGTAGC 1566 GGAATGTCCC 1567 CCTGTATGCTGC 1568 GGATGGTAGCAGTCTAGGGATTAACTTCCTGTATGCTGCAACT
AGTCTAGGGA ATACCCAAAG AACTCATGAACT CATGAACTTGGCCATTCTTTGGGTATGGGACATTCC
TTAACT AA TGGC
MMP9 NM_004994 1569 GAGAACCAAT 1570 CACCCGAGTG 1571 ACAGGTATTCCT 1572 GAGAACCAATCTCACCGACAGGCAGCTGGCAGAGGAATACCT
CTCACCGACA TAACCATAGC CTGCCAGCTGCC GTACCGCTATGGTTACACTCGGGTG
MPPED2 NM_001584 1573 CCGACCAACC 1574 AGGGCATTTA 1575 ATTTGACCTTCC 1576 CCGACCAACCCTCCAATTATATTTGACCTTCCAAACCCACAGG
CTCCAATTA GAGCTTCAGG AAACCCACAGGG GTTCCTGAAGCTCTAAATGCCCT
A
MRC1 NM_002438 1577 CTTGACCTCA 1578 GGACTGCGGT 1579 CCAACCGCTGTT 1580 CTTGACCTCAGGACTCTGGATTGGACTTAACAGTCTGAGCTTC
GGACTCTGGA CACTCCAC GAAGCTCAGACT AACAGCGGTTGGCAGTGGAGTGACCGCAGTCC
TT
MRPL13 NM_014078 1581 TCCGGTTCCC 1582 GTGGAAAAAC 1583 CGGCTGGAAATT 1584 TCCGGTTCCCTTCGTTTAGGTCGGCTGGAAATTATGTCCTCCG
TTCGTTTAG TGCGGAAAAC ATGTCCTCCGTC TCGGTTTTCCGCAGTTTTTCCAC
MSH2 NM_000251 1585 GATGCAGAAT 1586 TCTTGGCAAG 1587 CAAGAAGATTTA 1588 GATGCAGAATTGAGGCAGACTTTACAAGAAGATTTACTTCGTC
TGAGGCAGAC TCGGTTAAGA CTTCGTCGATTC GATTCCCAGATCTTAACCGACTTGCCAAGA
CCAGA
MSH3 NM_002439 1589 TGATTACCAT 1590 CTTGTGAAAA 1591 TCCCAATTGTCG 1592 TGATTACCATCATGGCTCAGATTGGCTCCTATGTTCCTGCAGA
CATGGCTCAG TGCCATCCAC CTTCTTCTGCAG AGAAGCGACAATTGGGATTGTGGATGGCATTTTCACAAG
A
MSH6 NM_000179 1593 TCTATTGGGG 1594 CAAATTGCGA 1595 CCGTTACCAGCT 1596 TCTATTGGGGGATTGGTAGGAACCGTTACCAGCTGGAAATTCC
GATTGGTAGG GTGGTGAAAT GGAAATTCCTGA TGAGAATTTCACCACTCGCAATTTG
GA
MTA1 NM_004689 1597 CCGCCCTCAC 1598 GGAATAAGTT 1599 CCCAGTGTCCGC 1600 CCGCCCTCACCTGCAGAGAAACGCGCTCCTTGGCGGACACTG
CTGAAGAGA AGCCGCGCTT CAAGGAGCG GGGGAGGAGAGGAAGAAGCGCGGCTAACTTATTCC
CT
MTPN NM_145808 1601 GGTGGAAGGA 1602 CAGCAGCAGA 1603 AAGCTGCCCACA 1604 GGTGGAAGGAAACCTCTTCATTATGCAGCAGATTGTGGGCAGC
AACCTCTTCA AATTCCAGG ATCTGCTGCATA TTGAAATCCTGGAATTTCTGCTGCTG
MTSS1 NM_014751 1605 TTCGACAAGT 1606 CTTGGAACAT 1607 CCAAGAAACAGC 1608 TTCGACAAGTCCTCCACCATTCCAAGAAACAGCGACATCAGCC
CCTCCACCAT CCGTCGGTAG GACATCAGCCAG AGTCCTACCGACGGATGTTCCAAG
MUC1 NM_002456 1609 GGCCAGGATC 1610 CTCCACGTCG 1611 CTCTGGCCTTCC 1612 GGCCAGGATCTGTGGTGGTACAATTGACTCTGGCCTTCCGAG
TGTGGTGGTA TGGACATTGA GAGAAGGTACC AAGGTACCATCAATGTCCACGACGTGGAG
MVP NM_017458 1613 ACGAGAACGA 1614 GCATGTAGGT 1615 CGCACCTTTCCG 1616 ACGAGAACGAGGGCATCTATGTGCAGGATGTCAAGACCGGAA
GGGCATCTAT GCTTCCAATC GTCTTGACATCC AGGTGCGCGCTGTGATTGGAAGCACCTACATGC
GT AC T
MYBL2 NM_002466 1617 GCCGAGATCG 1618 CTTTTGATGG 1619 CAGCATTGTCTG 1620 GCCGAGATCGCCAAGATGTTGCCAGGGAGGACAGACAATGCT
CCAAGATG TAGAGTTCCA TCCTCCCTGGCA GTGAAGAATCACTGGAACTCTACCATCAAAAG
GTGATTC
MYBPC1 NM_002465 1621 CAGCAACCAG 1622 CAGCAGTAAG 1623 AAATTCGCAAGC 1624 CAGCAACCAGGGAGTCTGTACCCTGGAAATTCGCAAGCCCAG
GGAGTCTGTA TGCCTCCATC CCAGCCCCTAT CCCCTATGATGGAGGCACTTACTGCTG
MYC NM_002467 1625 TCCCTCCACT 1626 CGGTTGTTGC 1627 TCTGACACTGTC 1628 TCCCTCCACTCGGAAGGACTATCCTGCTGCCAAGAGGGTCAA
CGGAAGGACT TGATCTGTCT CAACTTGACCCT GTTGGACAGTGTCAGAGTCCTGAGACAGATCAGCAACAACCG
A CA CTT
MYLK3 NM_182493 1629 CACCTGACTG 1630 GATGTAGTGC 1631 CACACCCTCACA 1632 CACCTGACTGAGCTGGATGTGGTCCTGTTCACCAGGCAGATCT
AGCTGGATGT TGGTGCAGGT GATCTGCCTGGT GTGAGGGTGTGCATTACCTGCACCAGCACTACATC
MYO6 NM_004999 1633 AAGCAGTTCT 1634 GATGAGCTCG 1635 CAATCCTCAGGG 1636 AAGCAGTTCTGGAGCAGGAGCGCAGGGACCGGGAGCTGGCC
GGAGCAGGAG GCTTCACTCT CCAGCTCCC CTGAGGATTGCCCAGAGTGAAGCCGAGCTCATC
NCAM1 NM_000615 1637 TAGTTCCCAG 1638 CAGCCTTGTT 1639 CTCAGCCTCGTC 1640 TAGTTCCCAGCTGACCATCAAAAAGGTGGATAAGAACGACGAG
CTGACCATCA CTCAGCAATG GTTCTTATCCAC GCTGAGTACATCTGCATTGCTGAGAACAAGGCTG
C
NCAPD3 NM_015261 1641 TCGTTGCTTA 1642 CTCCAGACAG 1643 CTACTGTCCGCA 1644 TCGTTGCTTAGACAAGGCGCCTACTGTCCGCAGCAAGGCACT
GACAAGGCG TGTGCAAAGC GCAAGGCACTGT GTCCAGCTTTGCACACTGTCTGGAG
NCOR1 NM_006311 1645 AACCGTTACA 1646 TCTGGAGAGA 1647 CCAGGCTCAGTC 1648 AACCGTTACAGCCCAGAATCCCAGGCTCAGTCTGTCCATCATC
GCCCAGAATC CCCTTGAACC TGTCCATCATCA AAAGACCAGGTTCAAGGGTCTCTCCAGA
NCOR2 NM_006312 1649 CGTCATCTAC 1650 GAGCACTGGG 1651 CCTCATAGGACA 1652 CGTCATCTACGAAGGCAAGAAGGGCCACGTCTTGTCCTATGA
GAAGGCAAGA TCACAGACAT AGACGTGGCCCT GGGTGGCATGTCTGTGACCCAGTGCTC
NDRG1 NM_006096 1653 AGGGCAACAT 1654 CAGTGCTCCT 1655 CTGCAAGGACAC 1656 AGGGCAACATTCCACAGCTGCCCTGGCTGTGATGAGTGTCCTT
TCCACAGC ACTCCGGC TCATCACAGCCA GCAGGGGCCGGAGTAGGAGCACTG
NDUFS5 NM_004552 1657 AGAAGAGTCA 1658 AGGCCGAACC 1659 TGTCCAAGAAAG 1660 AGAAGAGTCAAGGGCACGAGCATCGGGTAGCCATGCCTTTCT
AGGGCACGAG TTTTCTGG GCATGGCTACCC TGGACATCCAGAAAAGGTTCGGCCT
NEK2 NM_002497 1661 GTGAGGCAGC 1662 TGCCAATGGT 1663 TGCCTTCCCGGG 1664 GTGAGGCAGCGCGACTCTGGCGACTGGCCGGCCATGCCTTCC
GCGACTCT GTACAACACT CTGAGGACT CGGGCTGAGGACTATGAAGTGTTGTACACCATTGGCA
TCA
NETO2 NM_018092 1665 CCAGGGCACC 1666 AACGGTAAAT 1667 AGCCAACCCTTT 1668 CCAGGGCACCATACTGTTTCCAGCAGCCAACCCTTTTCTCCCA
ATACTGTTTC CAAGGTCTTC TCTCCCATCACA TCACAACTACGAAGACCTTGATTTACCGTT
GT
NEXN NM_144573 1669 AGGAGGAGGA 1670 GAGCTCCTGA 1671 TCATCTTCAGCA 1672 AGGAGGAGGAAGAAGGTAGCATCATGAATGGCTCCACTGCTG
AGAAGGTAGC TCTGGTTTGC GTGGAGCCATTC AAGATGAAGAGCAAACCAGATCAGGAGCTC
A A
NFAT5 NM_006599 1673 CTGAACCCCT 1674 AGGAAACGAT 1675 CGAGAATCAGTC 1676 CTGAACCCCTCTCCTGGTCACCGAGAATCAGTCCCCGTGGAG
CTCCTGGTC GGCGAGGT CCCGTGGAGTTC TTCCCCCTCCACCTCGCCATCGTTTCCT
NFATC2 NM_173091 1677 CAGTCAAGGT 1678 CTTTGGCTCG 1679 CGGGTTCCTACC 1680 CAGTCAAGGTCAGAGGCTGAGCCCGGGTTCCTACCCCACAGT
CAGAGGCTGA TGGCATTC CCACAGTCATTC CATTCAGCAGCAGAATGCCACGAGCCAAAG
G
NFKB1 NM_003998 1681 CAGACCAAGG 1682 AGCTGCCAGT 1683 AAGCTGTAAACA 1684 CAGACCAAGGAGATGGACCTCAGCGTGGTGCGGCTCATGTTT
AGATGGACCT GCTATCCG TGAGCCGCACCA ACAGCTTTTCTTCCGGATAGCACTGGCAGCT
NFKBIA NM_020529 1685 CTACTGGACG 1686 CCTTGACCAT 1687 CTCGTCTTTCAT 1688 CTACTGGACGACCGCCACGACAGCGGCCTGGACTCCATGAAA
ACCGCCAC CTGCTCGTAC GGAGTCCAGGCC GACGAGGAGTACGAGCAGATGGTCAAGG
T
NME1 NM_000269 1689 CCAACCCTGC 1690 ATGTATAATG 1691 CCTGGGACCATC 1692 CCAACCCTGCAGACTCCAAGCCTGGGACCATCCGTGGAGACT
AGACTCCAA TTCCTGCCAA CGTGGAGACTTC TCTGCATACAAGTTGGCAGGAACATTATACAT
CTTGTATG T
NNMT NM_006169 1693 CCTAGGGCAG 1694 CTAGTCCAGC 1695 CCCTCTCCTCAT 1696 CCTAGGGCAGGGATGGAGAGAGAGTCTGGGCATGAGGAGAG
GGATGGAG CAAACATCCC GCCCAGACTCTC GGTCTCGGGATGTTTGGCTGGACTAG
NOS3 NM_000603 1697 ATCTCCGCCT 1698 TCGGAGCCAT 1699 TTCACTCGCTTC 1700 ATCTCCGCCTCGCTCATGGGCACGGTGATGGCGAAGCGAGTG
CGCTCATG ACAGGATTGT GCCATCACCG AAGGCGACAATCCTGTATGGCTCCGA
C
NOX4 NM_016931 1701 CCTCAACTGC 1702 TGCTTGGAAC 1703 CCGAACACTCTT 1704 CCTCAACTGCAGCCTTATCCTTTTACCCATGTGCCGAACACTC
AGCCTTATCC CTTCTGTGAT GGCTTACCTCCG TTGGCTTACCTCCGAGGATCACAGAAGGTTCCAAGCA
NPBWR1 NM_005285 1705 TCACCAACCT 1706 GATGTTGATG 1707 ATCGCCGACGAG 1708 TCACCAACCTGTTCATCCTCAACCTGGCCATCGCCGACGAGCT
GTTCATCCTC GGCAGCAC CTCTTCACG CTTCACGCTGGTGCTGCCCATCAACATC
NPM1 NM_002520 1709 AATGTTGTCC 1710 CAAGCAAAGG 1711 AACAGGCATTTT 1712 AATGTTGTCCAGGTTCTATTGCCAAGAATGTGTTGTCCAAAAT
AGGTTCTATT GTGGAGTTC GGACAACACATT GCCTGTTTAGTTTTTAAAGATGGAACTCCACCCTTTGCTTG
GC CTTG
NRG1 NM_013957 1713 CGAGACTCTC 1714 CTTGGCGTGT 1715 ATGACCACCCCG 1716 CGAGACTCTCCTCATAGTGAAAGGTATGTGTCAGCCATGACCA
CTCATAGTGA GGAAATCTAC GCTCGTATGTCA CCCCGGCTCGTATGTCACCTGTAGATTTCCACACGCCAAG
AAGGTAT AG
NRIP3 NM_020645 1717 CCCACAAGCA 1718 TGCTCAATCT 1719 AGCTTTCTCTAC 1720 CCCACAAGCATGAAGGAGAAAAGCTTTCTCTACCCCGGCATCT
TGAAGGAGA GGCCCACTA CCCGGCATCTCA CAAAGTAGTGGGCCAGATTGAGCA
NRP1 NM_003873 1721 CAGCTCTCTC 1722 CCCAGCAGCT 1723 CAGGATCTACCC 1724 CAGCTCTCTCCACGCGATTCATCAGGATCTACCCCGAGAGAG
CACGCGATTC CCATTCTGA CGAGAGAGCCAC CCACTCATGGCGGACTGGGGCTCAGAATGGAGCTGCTGGG
TCAT
NUP62 NM_153719 1725 AGCCTCTTTG 1726 CTGTGGTCAC 1727 TCATCTGCCACC 1728 AGCCTCTTTGCGTCAATAGCAACTGCTCCAACCTCATCTGCCA
CGTCAATAGC AGGGGTACAG ACTGGACTCTCC CCACTGGACTCTCCCTCTGTACCCCTGTGACCACAG
OAZ1 NM_004152 1729 AGCAAGGACA 1730 GAAGACATGG 1731 CTGCTCCTCAGC 1732 AGCAAGGACAGCTTTGCAGTTCTCCTGGAGTTCGCTGAGGAG
GCTTTGCAGT TCGGCTCG GAACTCCAGGAG CAGCTGCGAGCCGACCATGTCTTC
OCLN NM_002538 1733 CCCTCCCATC 1734 GACGCGGGAG 1735 CTCCTCCCTCGG 1736 CCCTCCCATCCGAGTTTCAGGTGAATTGGTCACCGAGGGAGG
CGAGTTTC TGTAGGTG TGACCAATTCAC AGGCCGACACACCACACCTACACTCCCGCGTC
ODC1 NM_002539 1737 AGAGATCACC 1738 CGGGCTCAGC 1739 CCAGCGTTGGAC 1740 AGAGATCACCGGCGTAATCAACCCAGCGTTGGACAAATACTTT
GGCGTAATCA TATGATTCTC AAATACTTTCCG CCGTCAGACTCTGGAGTGAGAATCATAGCTGAGCCCG
A A TCA
OLFML2B NM_015441 1741 CATGTTGGAA 1742 CACCAGTTTG 1743 TGGCCTGGATCT 1744 CATGTTGGAAGGAGCGTTCTATGGCCTGGATCTCCTGAAGCTA
GGAGCGTTCT GTGGTGACTG CCTGAAGCTACA CATTCAGTCACCACCAAACTGGTG
OLFML3 NM_020190 1745 TCAGAACTGA 1746 CCAGATAGTC 1747 CAGACGATCCAC 1748 TCAGAACTGAGGCCGACACCATCTCCGGGAGAGTGGATCGTC
GGCCGACAC TACCTCCCGC TCTCCCGGAGAT TGGAGCGGGAGGTAGACTATCTGG
T
OMD NM_005014 1749 CGCAAACTCA 1750 CAGTCACAGC 1751 TCCGATGCACAT 1752 CGCAAACTCAAGACTATCCCAAATATTCCGATGCACATTCAGC
AGACTATCCC CTCAATTTCA TCAGCAACTCTA AACTCTACCTTCAGTTCAATGAAATTGAGGCTGTGACTG
A TT CC
OR51E1 NM_152430 1753 GCATGCTTTC 1754 AGAAGATGGC 1755 TCCTCATCTCCA 1756 GCATGCTTTCAGGCATTGACATCCTCATCTCCACCTCATCCAT
AGGCATTGA CAGCATTTTG CCTCATCCATGC GCCCAAAATGCTGGCCATCTTCT
OR51E2 NM_030774 1757 TATGGTGCCA 1758 GTCCTTGTCA 1759 ACATAGCCAGCA 1760 TATGGTGCCAAAACCAAACAGATCAGAACACGGGTGCTGGCT
AAACCAAACA CAGCTGATCT CCCGTGTTCTGA ATGTTCAAGATCAGCTGTGACAAGGAC
TG
OSM NM_020530 1761 GTTTCTGAAG 1762 AGGTGTCTGG 1763 CTGAGCTGGCCT 1764 GTTTCTGAAGGGGAGGTCACAGCCTGAGCTGGCCTCCTATGC
GGGAGGTCAC TTTGGGACA CCTATGCCTCAT CTCATCATGTCCCAAACCAGACACCT
PAGE1 NM_003785 1765 CAACCTGACG 1766 CAGATGCTCC 1767 CCAACTCAAAGT 1768 CAACCTGACGAAGTGGAATCACCAACTCAAAGTCAGGATTCTA
AAGTGGAATC CTCATCCTCT CAGGATTCTACA CACCTGCTGAAGAGAGAGAGGATGAGGGAGCATCTG
CCTGC
PAGE4 NM_007003 1769 GAATCTCAGC 1770 GTTCTTCGAT 1771 CCAACTGACAAT 1772 GAATCTCAGCAAGAGGAACCACCAACTGACAATCAGGATATTG
AAGAGGAACC CGGAGGTGTT CAGGATATTGAA AACCTGGACAAGAGAGAGAAGGAACACCTCCGATCGAAGAAC
A CCTGG
PAK6 NM_020168 1773 CCTCCAGGTC 1774 GTCCCTTCAG 1775 AGTTTCAGGAAG 1776 CCTCCAGGTCACCCACAGCCAGTTTCAGGAAGGCTGCCCCTC
ACCCACAG GCCAGAACTT GCTGCCCCTCTC TCTCCCACTAAGTTCTGGCCTGAAGGGAC
PATE1 NM_138294 1777 TGGTAATCCC 1778 TCCACCTTAT 1779 CAGCACAGTTCT 1780 TGGTAATCCCTGGTTAACCTTCATGGGCTGCCTAAAGAACTGT
TGGTTAACCT GCCTTTCACA TTAGGCAGCCCA GCTGATGTGAAAGGCATAAGGTGGA
TC
PCA3 NR_015342 1781 CGTGATTGTC 1782 AGAAAGGGGA 1783 CTGAGATGCTCC 1784 CGTGATTGTCAGGAGCAAGACCTGAGATGCTCCCTGCCTTCAG
AGGAGCAAGA GATGCAGAGG CTGCCTTCAGTG TGTCCTCTGCATCTCCCCTTTCT
PCDHGB7 NM_018927 1785 CCCAGCGTTG 1786 GAAACGCCAG 1787 ATTCTTAAACAG 1788 CCCAGCGTTGAAGCAGATAAGAAGATTCTTAAACAGCAAGCCC
AAGCAGAT TCCGTGTT CAAGCCCCGCC CGCCCAACACGGACTGGCGTTTC
PCNA NM_002592 1789 GAAGGTGTTG 1790 GGTTTACACC 1791 ATCCCAGCAGGC 1792 GAAGGTGTTGGAGGCACTCAAGGACCTCATCAACGAGGCCTG
GAGGCACTCA GCTGGAGCTA CTCGTTGATGAG CTGGGATATTAGCTCCAGCGGTGTAAACC
AG A
PDE9A NM_ 1793 TTCCACAACT 1794 AGACTGCAGA 1795 TACATCATCTGG 1796 TTCCACAACTTCCGGCACTGCTTCTGCGTGGCCCAGATGATGT
001001570 TCCGGCAC GCCAGACCA GCCACGCAGAAG ACAGCATGGTCTGGCTCTGCAGTCT
PDGFRB NM_002609 1797 CCAGCTCTCC 1798 GGGTGGCTCT 1799 ATCAATGTCCCT 1800 CCAGCTCTCCTTCCAGCTACAGATCAATGTCCCTGTCCGAGTG
TTCCAGCTAC CACTTAGCTC GTCCGAGTGCTG CTGGAGCTAAGTGAGAGCCACCC
PECAM1 NM_000442 1801 TGTATTTCAA 1802 TTAGCCTGAG 1803 TTTATGAACCTG 1804 TGTATTTCAAGACCTCTGTGCACTTATTTATGAACCTGCCCTG
GACCTCTGTG GAATTGCTGT CCCTGCTCCCAC CTCCCACAGAACACAGCAATTCCTCAGGCTAA
CACTT GTT A
PEX10 NM_153818 1805 GGAGAAGTTC 1806 ATCTGTGTCC 1807 CTACCTTCGGCA 1808 GGAGAAGTTCCCTCCCCAGAAGCTCATCTACCTTCGGCACTAC
CCTCCCCAG AGGCCCAC CTACCGCTGAGC CGCTGAGCCGGCGCCCGGGTGGGCCTGGACACAGAT
PGD NM_002631 1809 ATTCCCATGC 1810 CTGGCTGGAA 1811 ACTGCCCTCTCC 1812 ATTCCCATGCCCTGTTTTACCACTGCCCTCTCCTTCTATGACG
CCTGTTTTAC GCATCTCAT TTCTATGACGGG GGTACAGACATGAGATGCTTCCAGCCAG
T
PGF NM_002632 1813 GTGGTTTTCC 1814 AGCAAGGGAA 1815 ATCTTCTCAGAC 1816 GTGGTTTTCCCTCGGAGCCCCCTGGCTCGGGACGTCTGAGAA
CTCGGAGC CAGCCTCAT GTCCCGAGCCAG GATGCCGGTCATGAGGCTGTTCCCTTGCT
PGK1 NM_000291 1817 AGAGCCAGTT 1818 CTGGGCCTAC 1819 TCTCTGCTGGGC 1820 AGAGCCAGTTGCTGTAGAACTCAAATCTCTGCTGGGCAAGGAT
GCTGTAGAAC ACAGTCCTTC AAGGATGTTCTG GTTCTGTTCTTGAAGGACTGTGTAGGCCCAG
TCAA A TTC
PGR NM_000926 1821 GATAAAGGAG 1822 TCACAAGTCC 1823 TAAATTGCCGTC 1824 GATAAAGGAGCCGCGTGTCACTAAATTGCCGTCGCAGCCGCA
CCGCGTGTCA GGCACTTGAG GCAGCCGCA GCCACTCAAGTGCCGGACTTGTGA
PHTF2 NM_020432 1825 GATATGGCTG 1826 GGTTTGGGTG 1827 ACAATCTGGCAA 1828 GATATGGCTGATGCTGCTCCTGGGAACTGTGCATTGCCAGATT
ATGCTGCTCC TTCTTGTGGA TGCACAGTTCCC GTTTCCACAAGAACACCCAAACC
PIK3C2A NM_002645 1829 ATACCAATCA 1830 CACACTAGCA 1831 TGTGCTGTGACT 1832 ATACCAATCACCGCACAAACCCAGGCTATTTGTTAAGTCCAGT
CCGCACAAAC TTTTCTCCGC GGACTTAACAAA CACAGCACAAAGAAACATATGCGGAGAAAATGCTAGTGTG
C ATA TAGCCT
PIK3CA NM_006218 1833 GTGATTGAAG 1834 GTCCTGCGTG 1835 TCCTGCTTCTCG 1836 GTGATTGAAGAGCATGCCAATTGGTCTGTATCCCGAGAAGCAG
AGCATGCCAA GGAATAGC GGATACAGACCA GATTTAGCTATTCCCACGCAGGAC
PIK3CG NM_002649 1837 GGAGAACTCA 1838 TGATGCTTAG 1839 TTCTGGACAATT 1840 GGAGAACTCAATGTCCATCTCCATTCTTCTGGACAATTACTGC
ATGTCCATCT GCAGGGCT ACTGCCACCCGA CACCCGATAGCCCTGCCTAAGCATCA
CC
PIM1 NM_002648 1841 CTGCTCAAGG 1842 GGATCCACTC 1843 TACACTCGGGTC 1844 CTGCTCAAGGACACCGTCTACACGGACTTCGATGGGACCCGA
ACACCGTCTA TGGAGGGC CCATCGAAGTCC GTGTATAGCCCTCCAGAGTGGATCC
PLA2G7 NM_005084 1845 CCTGGCTGTG 1846 TGACCCATGC 1847 TGGCAATACATA 1848 CCTGGCTGTGGTTTATCCTTTTGACTGGCAATACATAAATCCT
GTTTATCCTT TGATGATTTC AATCCTGTTGCC GTTGCCCATATGAAATCATCAGCATGGGTCA
CA
PLAU NM_002658 1849 GTGGATGTGC 1850 CTGCGGATCC 1851 AAGCCAGGCGTC 1852 GTGGATGTGCCCTGAAGGACAAGCCAGGCGTCTACACGAGAG
CCTGAAGGA AGGGTAAGAA TACACGAGAGTC TCTCACACTTCTTACCCTGGATCCGCAG
TCAC
PLAUR NM_002659 1853 CCCATGGATG 1854 CCGGTGGCTA 1855 CATTGACTGCCG 1856 CCCATGGATGCTCCTCTGAAGAGACTTTCCTCATTGACTGCCG
CTCCTCTGAA CCAGACATTG AGGCCCCATG AGGCCCCATGAATCAATGTCTGGTAGCCACCGG
PLG NM_000301 1857 GGCAAAATTT 1858 ATGTATCCAT 1859 TGCCAGGCCTGG 1860 GGCAAAATTTCCAAGACCATGTCTGGACTGGAATGCCAGGCCT
CCAAGACCAT GAGCGTGTGG GACTCTCA GGGACTCTCAGAGCCCACACGCTCATGGATACAT
PLK1 NM_005030 1861 AATGAATACA 1862 TGTCTGAAGC 1863 AACCCCGTGGCC 1864 AATGAATACAGTATTCCCAAGCACATCAACCCCGTGGCCGCCT
GTATTCCCAA ATCTTCTGGA GCCTCC CCCTCATCCAGAAGATGCTTCAGACA
GCACAT TGA
PLOD2 NM_000935 1865 CAGGGAGGTG 1866 TCTCCCAGGA 1867 TCCAGCCTTTTC 1868 CAGGGAGGTGGTTGCAAATTTCTAAGGTACAATTGCTCTATTG
GTTGCAAAT TGCATGAAG GTGGTGACTCAA AGTCACCACGAAAAGGCTGGAGCTTCATGCATCCTGGGAGA
PLP2 NM_002668 1869 CCTGATCTGC 1870 GCAGCAAGGA 1871 ACACCAGGCTAC 1872 CCTGATCTGCTTCAGTGCCTCCACACCAGGCTACTCCTCCCTG
TTCAGTGCC TCATCTCAAT TCCTCCCTGTCG TCGGTGATTGAGATGATCCTTGCTGC
C
PNLIPRP2 NM_005396 1873 TGGAGAAGGT 1874 CACGGCTTGG 1875 ACCCGTGCCTCC 1876 TGGAGAAGGTGAACTGCATCTGTGTGGACTGGAGGCACGGGT
GAACTGCATC GTGTACATT AGTCCACAC CCCGGGCAATGTACACCCAAGCCGTG
POSTN NM_006475 1877 GTGGCCCAAT 1878 TCACAGGTGC 1879 TTCTCCATCTGG 1880 GTGGCCCAATTAGGCTTGGCATCTGCTCTGAGGCCAGATGGA
TAGGCTTG CAGCAAAG CCTCAGAGCAGA GAATACACTTTGCTGGCACCTGTGA
PPAP2B NM_003713 1881 ACAAGCACCA 1882 CACGAAGAAA 1883 ACCAGGGCTCCT 1884 ACAAGCACCATCCCAGTGATGTTCTGGCAGGATTTGCTCAAGG
TCCCAGTGA ACTATGCAGC TGAGCAAATCCT AGCCCTGGTGGCCTGCTGCATAGTTTTCTTCGTG
AG
PPFIA3 NM_003660 1885 CCTGGAGCTC 1886 AGCCACATAG 1887 CACCCACTTTAC 1888 CCTGGAGCTCCGTTACTCTCAGGCACCCACTTTACCTTCTGGT
CGTTACTCTC GGATCCAGG CTTCTGGTGCCC GCCCACCTGGATCCCTATGTGGCT
PPP1R12A NM_002480 1889 CGGCAAGGGG 1890 TGCCTGGCAT 1891 CCGTTCTTCTTC 1892 CGGCAAGGGGTTGATATAGAAGCAGCTCGAAAGGAAGAAGAA
TTGATATAGA CTCTAAGCA CTTTCGAGCTGC CGGATCATGCTTAGAGATGCCAGGCA
PPP3CA NM_000944 1893 ATACTCCGAG 1894 GGAAGCCTGT 1895 TACATGCGGTAC 1896 ATACTCCGAGCCCACGAAGCCCAAGATGCAGGGTACCGCATG
CCCACGAA TGTTTGGC CCTGCATCTTGG TACAGGAAAAGCCAAACAACAGGCTTCC
PRIMA1 NM_178013 1897 ATCCTCTTCC 1898 CCCAGCTGAG 1899 TGACGCATCCAG 1900 ATCCTCTTCCCTGAGCCGCTGACGCATCCAGGGCTCTAGTCTG
CTGAGCCG AGGGAATTTA GGCTCTAGTCTG CACATAAATTCCCTCTCAGCTGGG
PRKAR1B NM_002735 1901 ACAAAACCAT 1902 TGTCATCCAG 1903 AAGGCCATCTCC 1904 ACAAAACCATGACTGCGCTGGCCAAGGCCATCTCCAAGAACG
GACTGCGCT GTGAGCGA AAGAACGTGCTC TGCTCTTCGCTCACCTGGATGACA
PRKAR2B NM_002736 1905 TGATAATCGT 1906 GCACCAGGAG 1907 CGAACTGGCCTT 1908 TGATAATCGTGGGAGTTTCGGCGAACTGGCCTTAATGTACAAT
GGGAGTTTCG AGGTAGCAGT AATGTACAATAC ACACCCAGAGCAGCTACAATCACTGCTACCTCTCCTGGTGC
ACCCA
PRKCA NM_002737 1909 CAAGCAATGC 1910 GTAAATCCGC 1911 CAGCCTCTGCGG 1912 CAAGCAATGCGTCATCAATGTCCCCAGCCTCTGCGGAATGGAT
GTCATCAATG CCCCTCTTCT AATGGATCACAC CACACTGAGAAGAGGGGGCGGATTTAC
T T
PRKCB NM_002738 1913 GACCCAGCTC 1914 CCCATTCACG 1915 CCAGACCATGGA 1916 GACCCAGCTCCACTCCTGCTTCCAGACCATGGACCGCCTGTA
CACTCCTG TACTCCATCA CCGCCTGTACTT CTTTGTGATGGAGTACGTGAATGGG
PROM1 NM_006017 1917 CTATGACAGG 1918 CTCCAACCAT 1919 ACCCGAGGCTGT 1920 CTATGACAGGCATGCCACCCCGACCACCCGAGGCTGTGTCTC
CATGCCACC GAGGAAGACG GTCTCCAACAC CAACACCGGAGGCGTCTTCCTCATGGTTGGAG
PROS1 NM_000313 1921 GCAGCACAGG 1922 CCCACCTATC 1923 CTCATCCTGACA 1924 GCAGCACAGGAATCTTCTTCTTGGCAGCTGCAGTCTGTCAGGA
AATCTTCTTC CAACCTAATC GACTGCAGCTGC TGAGATATCAGATTAGGTTGGATAGGTGGG
TT TG
PSCA NM_005672 1925 ACCGTCATCA 1926 CGTGATGTTC 1927 CCTGTGAGTCAT 1928 ACCGTCATCAGCAAAGGCTGCAGCTTGAACTGCGTGGATGAC
GCAAAGGCT TTCTTGCCC CCACGCAGTTCA TCACAGGACTACTACGTGGGCAAGAAGAACATCACG
PSMD13 NM_002817 1929 GGAGGAGCTC 1930 CGGATCCTGC 1931 CCTGAAGTGTCA 1932 GGAGGAGCTCTACACGAAGAAGTTGTGGCATCAGCTGACACT
TACACGAAGA ACAAAATCA GCTGATGCCACA TCAGGTGCTTGATTTTGTGCAGGATCCG
AG
PTCH1 NM_000264 1933 CCACGACAAA 1934 TACTCGATGG 1935 CCTGAAACAAGG 1936 CCACGACAAAGCCGACTACATGCCTGAAACAAGGCTGAGAAT
GCCGACTAC GCTCTGCTG CTGAGAATCCCG CCCGGCAGCAGAGCCCATCGAGTA
PTEN NM_000314 1937 TGGCTAAGTG 1938 TGCACATATC 1939 CCTTTCCAGCTT 1940 TGGCTAAGTGAAGATGACAATCATGTTGCAGCAATTCACTGTA
AAGATGACAA ATTACACCAG TACAGTGAATTG AAGCTGGAAAGGGACGAACTGGTGTAATGATATGTGCA
TCATG TTCGT CTGCA
PTGER3 NM_000957 1941 TAACTGGGGC 1942 TTGCAGGAAA 1943 CCTTTGCCTTCC 1944 TAACTGGGGCAACCTTTTCTTCGCCTCTGCCTTTGCCTTCCTG
AACCTTTTCT AGGTGACTGT TGGGGCTCTT GGGCTCTTGGCGCTGACAGTCACCTTTTCCTGCAA
PTGS2 NM_000963 1945 GAATCATTCA 1946 CTGTACTGCG 1947 CCTACCACCAGC 1948 GAATCATTCACCAGGCAAATTGCTGGCAGGGTTGCTGGTGGTA
CCAGGCAAAT GGTGGAACAT AACCCTGCCA GGAATGTTCCACCCGCAGTACAG
TG
PTH1R NM_000316 1949 CGAGGTACAA 1950 GCGTGCCTTT 1951 CCAGTGCCAGTG 1952 CGAGGTACAAGCTGAGATCAAGAAATCTTGGAGCCGCTGGAC
GCTGAGATCA CGCTTGAA TCCAGCGGCT ACTGGCACTGGACTTCAAGCGAAAGGCACGC
AGAA
PTHLH NM_002820 1953 AGTGACTGGG 1954 AAGCCTGTTA 1955 TGACACCTCCAC 1956 AGTGACTGGGAGTGGGCTAGAAGGGGACCACCTGTCTGACAC
AGTGGGCTAG CCGTGAATCG AACGTCGCTGGA CTCCACAACGTCGCTGGAGCTCGATTCACGGTAACAGGCTT
AA A
PTK2 NM_005607 1957 GACCGGTCGA 1958 CTGGACATCT 1959 ACCAGGCCCGTC 1960 GACCGGTCGAATGATAAGGTGTACGAGAATGTGACGGGCCTG
ATGATAAGGT CGATGACAGC ACATTCTCGTAC GTGAAAGCTGTCATCGAGATGTCCAG
PTK2B NM_004103 1961 CAAGCCCAGC 1962 GAACCTGGAA 1963 CTCCGCAAACCA 1964 CAAGCCCAGCCGACCTAAGTACAGACCCCCTCCGCAAACCAA
CGACCTAAG CTGCAGCTTT ACCTCCTGGCT CCTCCTGGCTCCAAAGCTGCAGTTCCAGGTTC
G
PTK6 NM_005975 1965 GTGCAGGAAA 1966 GCACACACGA 1967 AGTGTCTGCGTC 1968 GTGCAGGAAAGGTTCACAAATGTGGAGTGTCTGCGTCCAATAC
GGTTCACAAA TGGAGTAAGG CAATACACGCGT ACGCGTGTGCTCCTCTCCTTACTCCATCGTGTGTGC
PTK7 NM_002821 1969 TCAGAGGACT 1970 CATACACCTC 1971 CGCAAGGTCCCA 1972 TCAGAGGACTCACGGTTCGAGGTCTTCAAGAATGGGACCTTGC
CACGGTTCG CACGCTGTTG TTCTTGAAGACC GCATCAACAGCGTGGAGGTGTATG
PTPN1 NM_002827 1973 AATGAGGAAG 1974 CTTCGATCAC 1975 CTGATCCAGACA 1976 AATGAGGAAGTTTCGGATGGGGCTGATCCAGACAGCCGACCA
TTTCGGATGG AGCCAGGTAG GCCGACCAGCT GCTGCGCTTCTCCTACCTGGCTGTGATCGAAG
PTPRK NM_002844 1977 TCAAACCCTC 1978 AGCAGCCAGT 1979 CCCCATCGTTGT 1980 TCAAACCCTCCCAGTGCTGGCCCCATCGTTGTACATTGCAGTG
CCAGTGCT TCGTCCAG ACATTGCAGTGC CTGGTGCTGGACGAACTGGCTGCT
PTTG1 NM_004219 1981 GGCTACTCTG 1982 GCTTCAGCCC 1983 CACACGGGTGCC 1984 GGCTACTCTGATCTATGTTGATAAGGAAAATGGAGAACCAGGC
ATCTATGTTG ATCCTTAGCA TGGTTCTCCA ACCCGTGTGGTTGCTAAGGATGGGCTGAAGC
ATAAGGAA
PYCARD NM_013258 1985 CTTTATAGAC 1986 AGCATCCAGC 1987 ACGTTTGTGACC 1988 CTTTATAGACCAGCACCGGGCTGCGCTTATCGCGAGGGTCAC
CAGCACCGGG AGCCACTC CTCGCGATAAGC AAACGTTGAGTGGCTGCTGGATGCT
RAB27A NM_004580 1989 TGAGAGATTA 1990 CCGGATGCTT 1991 ACAAATTGCTTC 1992 TGAGAGATTAATGGGCATTGTGTACAAATTGCTTCTCACCATC
ATGGGCATTG TATTCGTAGG TCACCATCCCCA CCCATTAGACCTACGAATAAAGCATCCGG
TG TT
RAB30 NM_014488 1993 TAAAGGCTGA 1994 CTCCCCAGCA 1995 CCATCAGGGCAG 1996 TAAAGGCTGAGGCACGGAGAAGAAAAGGAATCAGCAACTGCC
GGCACGGA TCTCATGG TTGCTGATTCCT CTGATGGGCCATGAGATGCTGGGGAG
RAB31 NM_006868 1997 CTGAAGGACC 1998 ATGCAAAGCC 1999 CTTCTCAAAGTG 2000 CTGAAGGACCCTACGCTCGGTGGCCTGGCACCTCACTTTGAG
CTACGCTCG AGTGTGCTC AGGTGCCAGGCC AAGAGTGAGCACACTGGCTTTGCAT
RAD21 NM_006265 2001 TAGGGATGGT 2002 TCGCGTACAC 2003 CACTTAAAACGA 2004 TAGGGATGGTATCTGAAACAACAATGGTCACCCTCTTGAGATT
ATCTGAAACA CTCTGCTC ATCTCAAGAGGG CGTTTTAAGTGTAATTCCATAATGAGCAGAGGTGTACGCGA
ACA TGACCA
RAD51 NM_002875 2005 AGACTACTCG 2006 AGCATCCGCA 2007 CTTTCAGCCAGG 2008 AGACTACTCGGGTCGAGGTGAGCTTTCAGCCAGGCAGATGCA
GGTCGAGGTG GAAACCTG CAGATGCACTTG CTTGGCCAGGTTTCTGCGGATGCT
RAD9A NM_004584 2009 GCCATCTTCA 2010 CGGTGTCTGA 2011 CTTTGCTGGACG 2012 GCCATCTTCACCATCAAGGACTCTTTGCTGGACGGCCACTTTG
CCATCAAGG GAGTGTGGC GCCACTTTGTCT TCTTGGCCACACTCTCAGACACCG
RAF1 NM_002880 2013 CGTCGTATGC 2014 TGAAGGCGTG 2015 TCCAGGATGCCT 2016 CGTCGTATGCGAGAGTCTGTTTCCAGGATGCCTGTTAGTTCTC
GAGAGTCTGT AGGTGTAGAA GTTAGTTCTCAG AGCACAGATATTCTACACCTCACGCCTTCA
CA
RAGE NM_014226 2017 ATTAGGGGAC 2018 GGGTGGAGAT 2019 CCGGAGTGTCTA 2020 ATTAGGGGACTTTGGCTCCTGCCGGAGTGTCTATTCCAAGCAG
TTTGGCTCCT GTATTCCGTG TTCCAAGCAGCC CCGTACACGGAATACATCTCCACCC
RALA NM_005402 2021 TGGTCCTGAA 2022 CCCCATTTCA 2023 TTGTGTTTCTTG 2024 TGGTCCTGAATGTAGCGTGTAAGCTTGTGTTTCTTGGGCAGTC
TGTAGCGTGT CCTCTTCAAT GGCAGTCTTTCT TTTCTTGAAATTGAAGAGGTGAAATGGGG
TGAA
RALBP1 NM_006788 2025 GGTGTCAGAT 2026 TTCGATATTG 2027 TGCTGTCCTGTC 2028 GGTGTCAGATATAAATGTGCAAATGCCTTCTTGCTGTCCTGTC
ATAAATGTGC CCAGCAGCTA GGTCTCAGTACG GGTCTCAGTACGTTCACTTTATAGCTGCTGGCAATATCGAA
AAATGC TAAA TTCA
RAP1B NM_ 2029 TGACAGCGTG 2030 CTGAGCCAAG 2031 CACGCATGATGC 2032 TGACAGCGTGAGAGGTACTAGGTTTTGACAAGCTTGCATCATG
001010942 AGAGGTACTA AACGACTAGC AAGCTTGTCAAA CGTGAGTATAAGCTAGTCGTTCTTGGCTCAG
GG TT
RARB NM_000965 2033 ATGAACCCTT 2034 GAGCTGGGTG 2035 TGTGCTCTGCTG 2036 ATGAACCCTTGACCCCAAGTTCAAGTGGGAACACAGCAGAGC
GACCCCAAGT AGATGCTAGG TGTTCCCACTTG ACAGTCCTAGCATCTCACCCAGCTC
RASSF1 NM_007182 2037 AGGGCACGTG 2038 AAAGAGTGCA 2039 CACCACCAAGAA 2040 AGGGCACGTGAAGTCATTGAGGCCCTGCTGCGAAAGTTCTTG
AAGTCATTG AACTTGCGG CTTTCGCAGCAG GTGGTGGATGACCCCCGCAAGTTTGCACTCTTT
RB1 NM_000321 2041 CGAAGCCCTT 2042 GGACTCTTCA 2043 CCCTTACGGATT 2044 CGAAGCCCTTACAAGTTTCCTAGTTCACCCTTACGGATTCCTG
ACAAGTTTCC GGGGTGAAAT CCTGGAGGGAAC GAGGGAACATCTATATTTCACCCCTGAAGAGTCC
RECK NM_021111 2045 GTCGCCGAGT 2046 GTGGGATGAT 2047 TCAAGTGTCCTT 2048 GTCGCCGAGTGTGCTTCTGTCAAGTGTCCTTCGCTCTTGGCAG
GTGCTTCT GGGTTTGC CGCTCTTGGCAG CTGGATGCAAACCCATCATCCCAC
REG4 NM_032044 2049 TGCTAACTCC 2050 TGCTAGGTTT 2051 TCCTCTTCCTTT 2052 TGCTAACTCCTGCACAGCCCCGTCCTCTTCCTTTCTGCTAGCC
TGCACAGCC CCCCTCTGAA CTGCTAGCCTGG TGGCTAAATCTGCTCATTATTTCAGAGGGGAAACCTAGCA
C
RELA NM_021975 2053 CTGCCGGGAT 2054 CCAGGTTCTG 2055 CTGAGCTCTGCC 2056 CTGCCGGGATGGCTTCTATGAGGCTGAGCTCTGCCCGGACCG
GGCTTCTAT GAAACTGTGG CGGACCGCT CTGCATCCACAGTTTCCAGAACCTGG
AT
RFX1 NM_002918 2057 TCCTCTCCAA 2058 CAGGCCCTGG 2059 TCCAATGGACCA 2060 TCCTCTCCAAGTTCGAGCCCGTGCTCCAATGGACCAAGCACTG
GTTCGAGCC TACAGCAC AGCACTGTGACA TGACAACGTGCTGTACCAGGGCCTG
RGS10 NM_ 2061 AGACATCCAC 2062 CCATTTGGCT 2063 AGTTCCAGCAGC 2064 AGACATCCACGACAGCGATGGCAGTTCCAGCAGCAGCCACCA
001005339 GACAGCGAT GTGCTCTTG AGCCACCAGAG GAGCCTCAAGAGCACAGCCAAATGG
RGS7 NM_002924 2065 CAGGCTGCAG 2066 TTTGCTTGTG 2067 TGAAAATGAACT 2068 CAGGCTGCAGAGAGCATTTGCCCGGAAGTGGGAGTTCATTTTC
AGAGCATTT CTTCTGCTTG CCCACTTCCGGG ATGCAAGCAGAAGCACAAGCAAA
RHOA NM_001664 2069 TGGCATAGCT 2070 TGCCACAGCT 2071 AAATGGGCTCAA 2072 TGGCATAGCTCTGGGGTGGGCAGTTTTTTGAAAATGGGCTCAA
CTGGGGTG GCATGAAC CCAGAAAAGCCC CCAGAAAAGCCCAAGTTCATGCAGCTGTGGCA
RHOB NM_004040 2073 AAGCATGAAC 2074 CCTCCCCAAG 2075 CTTTCCAACCCC 2076 AAGCATGAACAGGACTTGACCATCTTTCCAACCCCTGGGGAAG
AGGACTTGAC TCAGTTGC TGGGGAAGACAT ACATTTGCAACTGACTTGGGGAGG
C
RHOC NM_175744 2077 CCCGTTCGGT 2078 GAGCACTCAA 2079 TCCGGTTCGCCA 2080 CCCGTTCGGTCTGAGGAAGGCCGGGACATGGCGAACCGGATC
CTGAGGAA GGTAGCCAAA TGTCCCG AGTGCCTTTGGCTACCTTGAGTGCTC
GG
RLN1 NM_006911 2081 AGCTGAAGGC 2082 TTGGAATCCT 2083 TGAGAGGCAACC 2084 AGCTGAAGGCAGCCCTATCTGAGAGGCAACCATCATTACCAG
AGCCCTATC TTAATGCAGG ATCATTACCAGA AGCTACAGCAGTATGTACCTGCATTAAAGGATTCCAA
T GC
RND3 NM_005168 2085 TCGGAATTGG 2086 CTGGTTACTC 2087 TTTTAAGCCTGA 2088 TCGGAATTGGACTTGGGAGGCGCGGTGAGGAGTCAGGCTTAA
ACTTGGGAG CCCTCCAACA CTCCTCACCGCG AACTTGTTGGAGGGGAGTAACCAG
RNF114 NM_018683 2089 TGACAGGGGA 2090 GGAAGACAGC 2091 CCAGGTCAGCCC 2092 TGACAGGGGAAGTGGGTCCCCAGGTCAGCCCTTCTCTTCCCT
AGTGGGTC TTTGGCAAGA TTCTCTTCCCTT TTGGGCTCTTGCCAAAGCTGTCTTCC
ROBO2 NM_002942 2093 CTACAAGGCC 2094 CACCAGTGGC 2095 CTGTACCATCCA 2096 CTACAAGGCCCAGCCAACCAAACGCTGGCAGTGGATGGTACA
CAGCCAAC TTTACATTTC CTGCCAGCGTTT GCGTTACTGAAATGTAAAGCCACTGGTG
AG
RRM1 NM_001033 2097 GGGCTACTGG 2098 CTCTCAGCAT 2099 CATTGGAATTGC 2100 GGGCTACTGGCAGCTACATTGCTGGGACTAATGGCAATTCCAA
CAGCTACATT CGGTACAAGG CATTAGTCCCAG TGGCCTTGTACCGATGCTGAGAG
C
RRM2 NM_001034 2101 CAGCGGGATT 2102 ATCTGCGTTG 2103 CCAGCACAGCCA 2104 CAGCGGGATTAAACAGTCCTTTAACCAGCACAGCCAGTTAAAA
AAACAGTCCT AAGCAGTGAG GTTAAAAGATGC GATGCAGCCTCACTGCTTCAACGCAGAT
A
S100P NM_005980 2105 AGACAAGGAT 2106 GAAGTCCACC 2107 TTGCTCAAGGAC 2108 AGACAAGGATGCCGTGGATAAATTGCTCAAGGACCTGGACGC
GCCGTGGATA TGGGCATCTC CTGGACGCCAA CAATGGAGATGCCCAGGTGGACTTC
A
SAT1 NM_002970 2109 CCTTTTACCA 2110 ACAATGCTGT 2111 TCCAGTGCTCTT 2112 CCTTTTACCACTGCCTGGTTGCAGAAGTGCCGAAAGAGCACTG
CTGCCTGGTT GTCCTTCCG TCGGCACTTCTG GACTCCGGAAGGACACAGCATTGT
SCUBE2 NM_020974 2113 TGACAATCAG 2114 TGTGACTACA 2115 CAGGCCCTCTTC 2116 TGACAATCAGCACACCTGCATTCACCGCTCGGAAGAGGGCCT
CACACCTGCA GCCGTGATCC CGAGCGGT GAGCTGCATGAATAAGGATCACGGCTGTAGTCACA
T TTA
SDC1 NM_002997 2117 GAAATTGACG 2118 AGGAGCTAAC 2119 CTCTGAGCGCCT 2120 GAAATTGACGAGGGGTGTCTTGGGCAGAGCTGGCTCTGAGCG
AGGGGTGTCT GGAGAACCTG CCATCCAAGG CCTCCATCCAAGGCCAGGTTCTCCGTTAGCTCCT
SDC2 NM_002998 2121 GGATTGAAGT 2122 ACCAGCCACA 2123 AACTCCATCTCC 2124 GGATTGAAGTGGCTGGAAAGAGTGATGCCTGGGGAAGGAGAT
GGCTGGAAAG GTACCCTCA TTCCCCAGGCAT GGAGTTATGAGGGTACTGTGGCTGGT
SDHC NM_003001 2125 CTTCCCTCGG 2126 TTCCCTCCTG 2127 TTACATCCTCCC 2128 CTTCCCTCGGGTCTCAGGCATTTACATCCTCCCTCTCCCCGCA
GTCTCAGG GTAAAGGTCA TCTCCCCGCAAT ATCTGACCTTTACCAGGAGGGAA
SEC14L1 NM_ 2129 AGGGTTCCCA 2130 GCAGGCATGC 2131 CGGGCTTCTACA 2132 AGGGTTCCCATGTGACCAGGTGGCCGGGCTTCTACATCCTGC
001039573 TGTGACCAG TGTGGAAT TCCTGCAGTGG AGTGGAAATTCCACAGCATGCCTGC
SEC23A NM_006364 2133 CGTGTGCATT 2134 CCCATTACCA 2135 TCCTGGAGATGA 2136 CGTGTGCATTAGATCAGACAGGTCTCCTGGAGATGAAATGCTG
AGATCAGACA TGTATCCTCC AATGCTGTCCCA TCCCAACCTTACTGGAGGATACATGGTAATGGG
GG AG
SEMA3A NM_006080 2137 TTGGAATGCA 2138 CTCTTCATTT 2139 TTGCCAATAGAC 2140 TTGGAATGCAGTCCGAAGTCGCAGAGAGCGCTGGTCTATTGG
GTCCGAAGT CGCCTCTGGA CAGCGCTCTCTG CAATTCCAGAGGCGAAATGAAGAG
SEPT9 NM_006640 2141 CAGTGACCAC 2142 CTTCGATGGT 2143 TTGCCAATAGAC 2144 CAGTGACCACGAGTACCAGGTCAACGGCAAGAGGATCCTTGG
GAGTACCAGG ACCCCACTTG CAGCGCTCTCTG GAGGAAGACCAAGTGGGGTACCATCGAAG
SERPINA3 NM_001085 2145 GTGTGGCCCT 2146 CCCTGTGCAT 2147 AGGGAATCGCTG 2148 GTGTGGCCCTGTCTGCTTATCCTTGGAAGGTGACAGCGATTCC
GTCTGCTTA GTGAGAGCTA TCACCTTCCAAG CTGTGTAGCTCTCACATGCACAGGG
C
SERPINB5 NM_002639 2149 CAGATGGCCA 2150 GGCAGCATTA 2151 AGCTGACAACAG 2152 CAGATGGCCACTTTGAGAACATTTTAGCTGACAACAGTGTGAA
CTTTGAGAAC ACCACAAGGA TGTGAACGACCA CGACCAGACCAAAATCCTTGTGGTTAATGCTGCC
ATT TT GACC
SESN3 NM_144665 2153 GACCCTGGTT 2154 GAGCTCGGAA 2155 TGCTCTTCTCCT 2156 GACCCTGGTTTTGGGTATGAAGACTTTGCCAGACGAGGAGAA
TTGGGTATGA TGTTGGCA CGTCTGGCAAAG GAGCATTTGCCAACATTCCGAGCTC
SFRP4 NM_003014 2157 TACAGGATGA 2158 GTTGTTAGGG 2159 CCTGGGACAGCC 2160 TACAGGATGAGGCTGGGCATTGCCTGGGACAGCCTATGTAAG
GGCTGGGC CAAGGGGC TATGTAAGGCCA GCCATGTGCCCCTTGCCCTAACAAC
SH3RF2 NM_152550 2161 CCATCACAAC 2162 CACTGGGGTG 2163 AACCGGATGGTC 2164 CCATCACAACAGCCTTGAACACTCTCAACCGGATGGTCCATTC
AGCCTTGAAC CTGATCTCTA CATTCTCCTTCA TCCTTCAGGGCGCCATATGGTAGAGATCAGCACCCCAGTG
SH3YL1 NM_015677 2165 CCTCCAAAGC 2166 CTTTGAGAGC 2167 CACAGCAGTCAT 2168 CCTCCAAAGCCATTGTCAAGACCACAGCAGTCATCTGCACCAG
CATTGTCAAG CAGAGTTCAG CTGCACCAGTCC TCCAGCTGAACTCTGGCTCTCAAAG
C
SHH NM_000193 2169 GTCCAAGGCA 2170 GAAGCAGCCT 2171 CACCGAGTTCTC 2172 GTCCAAGGCACATATCCACTGCTCGGTGAAAGCAGAGAACTC
CATATCCACT CCCGATTT TGCTTTCACCGA GGTGGCGGCCAAATCGGGAGGCTGCTTC
G
SHMT2 NM_005412 2173 AGCGGGTGCT 2174 ATGGCACTTC 2175 CCATCACTGCCA 2176 AGCGGGTGCTAGAGCTTGTATCCATCACTGCCAACAAGAACAC
AGAGCTTGTA GGTCTCCA ACAAGAACACCT CTGTCCTGGAGACCGAAGTGCCAT
G
SIM2 NM_005069 2177 GATGGTAGGA 2178 CACAAGGAGC 2179 CGCCTCTCCACG 2180 GATGGTAGGAAGGGATGTGCCCGCCTCTCCACGCACTCAGCT
AGGGATGTGC TGTGAATGAG CACTCAGCTAT ATACCTCATTCACAGCTCCTTGTG
G
SIPA1L1 NM_015556 2181 CTAGGACAGC 2182 CATAACCGTA 2183 CGCCACAATGCC 2184 CTAGGACAGCTTGGCTTCCATGTCAACTATGAGGGCATTGTGG
TTGGCTTCCA GGGCTCCACA CTCATAGTTGAC CGGATGTGGAGCCCTACGGTTATG
SKIL NM_005414 2185 AGAGGCTGAA 2186 CTATCGGCCT 2187 CCAATCTCTGCC 2188 AGAGGCTGAATATGCAGGACAGTTGGCAGAACTGAGGCAGAG
TATGCAGGAC CAGCATGG TCAGTTCTGCCA ATTGGACCATGCTGAGGCCGATAG
A
SLC22A3 NM_021977 2189 ATCGTCAGCG 2190 CAGGATGGCT 2191 CAGCATCCACGC 2192 ATCGTCAGCGAGTTTGACCTTGTCTGTGTCAATGCGTGGATGC
AGTTTGACCT TGGGTGAG ATTGACACAGAC TGGACCTCACCCAAGCCATCCTG
SLC25A21 NM_030631 2193 AAGTGTTTTT 2194 GGCCGATCGA 2195 TCATGGTGCTGC 2196 AAGTGTTTTTCCCCCTTGAGATAATGGATATTTGCTATGCAGC
CCCCCTTGAG TAGTCTCTCT ATAGCAAATATC ACCATGAAGAAGAGAGACTATCGATCGGCC
AT T CA
SLC44A1 NM_080546 2197 AGGACCGTAG 2198 ATCCCATCCC 2199 TACCATGGCTGC 2200 AGGACCGTAGCTGCACAGACATACCATGGCTGCTGCTCTTCAT
CTGCACAGAC AATGCAGA TGCTCTTCATCC CCTCTTCTGCATTGGGATGGGAT
SMAD4 NM_005359 2201 GGACATTACT 2202 ACCAATACTC 2203 TGCATTCCAGCC 2204 GGACATTACTGGCCTGTTCACAATGAGCTTGCATTCCAGCCTC
GGCCTGTTCA AGGAGCAGGA TCCCATTTCCA CCATTTCCAATCATCCTGCTCCTGAGTATTGGT
CA TGA
SMARCC2 NM_003075 2205 TACCGACTGA 2206 GACATCACCC 2207 TATCTTACCTCT 2208 TACCGACTGAACCCCCAAGAGTATCTTACCTCTACCGCCTGCC
ACCCCCAA GCTAGGTTTC ACCGCCTGCCGC GCCGAAACCTAGCGGGTGATGTC
SMARCD1 NM_003076 2209 CCGAGTTAGC 2210 CCTTTGTGCC 2211 CCCACCCTTGCT 2212 CCGAGTTAGCATATCCCAGGCTCGCAGACTCAACACAGCAAG
ATATCCCAGG CAGCTGTC GTGTTGAGTCTG GGTGGGAGACAGCTGGGCACAAAGG
SMO NM_005631 2213 GGCATCCAGT 2214 CGCGATGTAG 2215 CTTCACAGAGGC 2216 GGCATCCAGTGCCAGAACCCGCTCTTCACAGAGGCTGAGCAC
GCCAGAAC CTGTGCAT TGAGCACCAGGA CAGGACATGCACAGCTACATCGCG
SNAI1 NM_005985 2217 CCCAATCGGA 2218 GTAGGGCTGC 2219 TCTGGATTAGAG 2220 CCCAATCGGAAGCCTAACTACAGCGAGCTGCAGGACTCTAAT
AGCCTAACTA TGGAAGGTAA TCCTGCAGCTCG CCAGAGTTTACCTTCCAGCAGCCCTAC
C
SNRPB2 NM_003092 2221 CGTTTCCTGC 2222 AGGTAGAAGG 2223 CCCACCTAAGGC 2224 CGTTTCCTGCTTTTGGTTCTTACAGTAGTCGGCGTAGGCCTTA
TTTTGGTTCT CGCACGAA CTACGCCGACTA GGTGGGTTCGTGCGCCTTCTACCT
SOD1 NM_000454 2225 TGAAGAGAGG 2226 AATAGACACA 2227 TTTGTCAGCAGT 2228 TGAAGAGAGGCATGTTGGAGACTTGGGCAATGTGACTGCTGA
CATGTTGGAG TCGGCCACAC CACATTGCCCAA CAAAGATGGTGTGGCCGATGTGTCTATT
SORBS1 NM_015385 2229 GCAGATGAGT 2230 AGCGAGTGAA 2231 ATTTCCATTGGC 2232 GCAGATGAGTGGAGGCTTTCTTCCAGTGCTGATGCCAATGGAA
GGAGGCTTTC GAGGGCTG ATCAGCACTGGA ATGCCCAGCCCTCTTCACTCGCT
SOX4 NM_003107 2233 AGATGATCTC 2234 GCGCCCTTCA 2235 CGAGTCCAGCAT 2236 AGATGATCTCGGGAGACTGGCTCGAGTCCAGCATCTCCAACC
GGGAGACTGG GTAGGTGA CTCCAACCTGGT TGGTTTTCACCTACTGAAGGGCGC
SPARC NM_003118 2237 TCTTCCCTGT 2238 AGCTCGGTGT 2239 TGGACCAGCACC 2240 TCTTCCCTGTACACTGGCAGTTCGGCCAGCTGGACCAGCACC
ACACTGGCAG GGGAGAGGTA CCATTGACGG CCATTGACGGGTACCTCTCCCACACCGAGCT
TTC
SPARCL1 NM_004684 2241 GGCACAGTGC 2242 GATTGAGCTC 2243 ACTTCATCCCAA 2244 GGCACAGTGCAAGTGATGACTACTTCATCCCAAGCCAGGCCTT
AAGTGATGA TCTCGGCCT GCCAGGCCTTTC TCTGGAGGCCGAGAGAGCTCAATC
SPDEF NM_012391 2245 CCATCCGCCA 2246 GGGTGCACGA 2247 ATCATCCGGAAG 2248 CCATCCGCCAGTATTACAAGAAGGGCATCATCCGGAAGCCAG
GTATTACAAG ACTGGTAGA CCAGACATCTCC ACATCTCCCAGCGCCTCGTCTACCAGTTCGTGCACCC
SPINK1 NM_003122 2249 CTGCCATATG 2250 GTTGAAAACT 2251 ACCACGTCTCTT 2252 CTGCCATATGACCCTTCCAGTCCCAGGCTTCTGAAGAGACGTG
ACCCTTCCAG GCACCGCAC CAGAAGCCTGGG GTAAGTGCGGTGCAGTTTTCAAC
SPINT1 NM_003710 2253 ATTCCCAGCA 2254 AGATGGCTAC 2255 CTGTCGCAGTGT 2256 ATTCCCAGCACAGGCTCTGTGGAGATGGCTGTCGCAGTGTTC
CAGGCTCTGT CACCACCACA TCCTGGTCATCT CTGGTCATCTGCATTGTGGTGGTGGTAGCCATCT
A GC
SPP1 NM_ 2257 TCACACATGG 2258 GTTCAGGTCC 2259 TGAATGGTGCAT 2260 TCACACATGGAAAGCGAGGAGTTGAATGGTGCATACAAGGCC
001040058 AAAGCGAGG TGGGCAAC ACAAGGCCATCC ATCCCCGTTGCCCAGGACCTGAAC
SOLE NM_003129 2261 ATTTTCGAGG 2262 CCTGAGCAAG 2263 TGGGCAAGAAAA 2264 ATTTTCGAGGCCAAAAAATCATTTTACTGGGCAAGAAAAACAT
CCAAAAAATC GATATTCACG ACATCTCATTCC CTCATTCCTTTGTCGTGAATATCCTTGCTCAGG
TTTG
SRC NM_005417 2265 TGAGGAGTGG 2266 CTCTCGGGTT 2267 AACCGCTCTGAC 2268 TGAGGAGTGGTATTTTGGCAAGATCACCAGACGGGAGTCAGA
TATTTTGGCA CTCTGCATTG TCCCGTCTGGTG GCGGTTACTGCTCAATGCAGAGAACCCGAGAG
AGA A
SRD5A1 NM_001047 2269 GGGCTGGAAT 2270 CCATGACTGC 2271 CCTCTCTCGGAG 2272 GGGCTGGAATCTGTCTAGGAGCCCTCTCTCGGAGGCCACAGA
CTGTCTAGGA ACAATGGCT GCCACAGAGGCT GGCTGGGGGTAGCCATTGTGCAGTCATGG
SRD5A2 NM_000348 2273 GTAGGTCTCC 2274 TCCCTGGAAG 2275 AGACACCACTCA 2276 GTAGGTCTCCTGGCGTTCTGCCAGCTGGCCTGGGGATTCTGA
TGGCGTTCTG GGTAGGAGTA GAATCCCCAGGC GTGGTGTCTGCTTAGAGTTTACTCCTACCCTTCCAGGGA
A
ST5 NM_005418 2277 CCTGTCCTGC 2278 CAGCTGCACA 2279 AGTCACGAGCAC 2280 CCTGTCCTGCCAGAGCATGGATGAAGTTTCGCTGGGTGCTCGT
CAGAGCAT AAACTGGC CCAGCGAAACTT GACTGGCCAGTTTTGTGCAGCTG
STAT1 NM_007315 2281 GGGCTCAGCT 2282 ACATGTTCAG 2283 TGGCAGTTTTCT 2284 GGGCTCAGCTTTCAGAAGTGCTGAGTTGGCAGTTTTCTTCTGT
TTCAGAAGTG CTGGTCCACA TCTGTCACCAAA CACCAAAAGAGGTCTCAATGTGGACCAGCTGAACATGT
A
STAT3 NM_003150 2285 TCACATGCCA 2286 CTTGCAGGAA 2287 TCCTGGGAGAGA 2288 TCACATGCCACTTTGGTGTTTCATAATCTCCTGGGAGAGATTG
CTTTGGTGTT GCGGCTATAC TTGACCAGCA ACCAGCAGTATAGCCGCTTCCTGCAAG
STAT5A NM_003152 2289 GAGGCGCTCA 2290 GCCAGGAACA 2291 CGGTTGCTCTGC 2292 GAGGCGCTCAACATGAAATTCAAGGCCGAAGTGCAGAGCAAC
ACATGAAATT CGAGGTTCTC ACTTCGGCCT CGGGGCCTGACCAAGGAGAACCTCGTGTTCCTGGC
C
STAT5B NM_012448 2293 CCAGTGGTGG 2294 GCAAAAGCAT 2295 CAGCCAGGACAA 2296 CCAGTGGTGGTGATCGTTCATGGCAGCCAGGACAACAATGCG
TGATCGTTCA TGTCCCAGAG CAATGCGACGG ACGGCCACTGTTCTCTGGGACAATGCTTTTGC
A
STMN1 NM_005563 2297 AATACCCAAC 2298 GGAGACAATG 2299 CACGTTCTCTGC 2300 AATACCCAACGCACAAATGACCGCACGTTCTCTGCCCCGTTTC
GCACAAATGA CAAACCACAC CCCGTTTCTTG TTGCCCCAGTGTGGTTTGCATTGTCTCC
STS NM_000351 2301 GAAGATCCCT 2302 GGATGATGTT 2303 CTGCGTGGCTCT 2304 GAAGATCCCTTTCCTCCTACTGTTCTTTCTGTGGGAAGCCGAG
TTCCTCCTAC CGGCCTTGAT CGGCTTCCCA AGCCACGCAGCATCAAGGCCGAACATCATCC
TGTTC
SULF1 NM_015170 2305 TGCAGTTGTA 2306 TCTCAAGAAT 2307 TACCGTGCCAGC 2308 TGCAGTTGTAGGGAGTCTGGTTACCGTGCCAGCAGAAGCCAA
GGGAGTCTGG TGCCGTTGAC AGAAGCCAAAG AGAAAGAGTCAACGGCAATTCTTGAGA
SUMO1 NM_003352 2309 GTGAAGCCAC 2310 CCTTCCTTCT 2311 CTGACCAGGAGG 2312 GTGAAGCCACCGTCATCATGTCTGACCAGGAGGCAAAACCTTC
CGTCATCATG TATCCCCCAA CAAAACCTTCAA AACTGAGGACTTGGGGGATAAGAAGGAAGG
GT CTGA
SVIL NM_003174 2313 ACTTGCCCAG 2314 GACACCATCC 2315 ACCCCAGGACTG 2316 ACTTGCCCAGCACAAGGAAGACCCCAGGACTGATGTCAAGGC
CACAAGGA GTGTCACATC ATGTCAAGGCAT ATACGATGTGACACGGATGGTGTC
TAF2 NM_003184 2317 GCGCTCCACT 2318 CTTGTGCTCA 2319 AGCCTCCAAACA 2320 GCGCTCCACTCTCAGTCTTTACTAAGGAATCTACAGCCTCCAA
CTCAGTCTTT TGGTGATGGT CAGTGACCACCA ACACAGTGACCACCATCACCACCATCACCATGAGCACAAG
TARP NM_ 2321 GAGCAACACG 2322 GGCACCGTTA 2323 TCTTCATGGTGT 2324 GAGCAACACGATTCTGGGATCCCAGGAGGGGAACACCATGAA
001003799 ATTCTGGGA ACCAGCTAAA TCCCCTCCTGG GACTAACGACACATACATGAAATTTAGCTGGTTAACGGTGCC
T
TBP NM_003194 2325 GCCCGAAACG 2326 CGTGGCTCTC 2327 TACCGCAGCAAA 2328 GCCCGAAACGCCGAATATAATCCCAAGCGGTTTGCTGCGGTA
CCGAATATA TTATCCTCAT CCGCTTGGG ATCATGAGGATAAGAGAGCCACG
GAT
TFDP1 NM_007111 2329 TGCGAAGTGC 2330 GCCTTCCAGA 2331 CGCACCAGCATG 2332 TGCGAAGTGCTTTTGTTTGTTTGTTTTCGTTTGGTTAAAGCTT
TTTTGTTTGT CAGTCTCCAT GCAATAAGCTTT ATTGCCATGCTGGTGCGGCTATGGAGACTGTCTGGAAGGC
TFF1 NM_003225 2333 GCCCTCCCAG 2334 CGTCGATGGT 2335 TGCTGTTTCGAC 2336 GCCCTCCCAGTGTGCAAATAAGGGCTGCTGTTTCGACGACAC
TGTGCAAAT ATTAGGATAG GACACCGTTCG CGTTCGTGGGGTCCCCTGGTGCTTCTATCCTAATACCATCGAC
AAGCA G
TFF3 NM_003226 2337 AGGCACTGTT 2338 CATCAGGCTC 2339 CAGAAGCGCTTG 2340 AGGCACTGTTCATCTCAGCTTTTCTGTCCCTTTGCTCCCGGCA
CATCTCAGTT CAGATATGAA CCGGGAGCAAAG AGCGCTTCTGCTGAAAGTTCATATCTGGAGCCTGATG
TTTCT CTTTC G
TGFA NM_003236 2341 GGTGTGCCAC 2342 ACGGAGTTCT 2343 TTGGCCTGTAAT 2344 GGTGTGCCACAGACCTTCCTACTTGGCCTGTAATCACCTGTGC
AGACCTTCCT TGACAGAGTT CACCTGTGCAGC AGCCTTTTGTGGGCCTTCAAAACTCTGTCAAGAACTCCGT
TTGA CTT
TGFB1I1 NM_ 2345 GCTACTTTGA 2346 GGTCACCATC 2347 CAAGATGTGGCT 2348 GCTACTTTGAGCGCTTCTCGCCAAGATGTGGCTTCTGCAACCA
001042454 GCGCTTCTCG TTGTGTCGG TCTGCAACCAGC GCCCATCCGACACAAGATGGTGACC
TGFB2 NM_003238 2349 ACCAGTCCCC 2350 CCTGGTGCTG 2351 TCCTGAGCCCGA 2352 ACCAGTCCCCCAGAAGACTATCCTGAGCCCGAGGAAGTCCCC
CAGAAGACTA TTGTAGATGG GGAAGTCCC CCGGAGGTGATTTCCATCTACAACAGCACCAGG
TGFB3 NM_003239 2353 GGATCGAGCT 2354 GCCACCGATA 2355 CGGCCAGATGAG 2356 GGATCGAGCTCTTCCAGATCCTTCGGCCAGATGAGCACATTGC
CTTCCAGATC TAGCGCTGTT CACATTGCC CAAACAGCGCTATATCGGTGGC
CT
TGFBR2 NM_003242 2357 AACACCAATG 2358 CCTCTTCATC 2359 TTCTGGGCTCCT 2360 AACACCAATGGGTTCCATCTTTCTGGGCTCCTGATTGCTCAAG
GGTTCCATCT AGGCCAAACT GATTGCTCAAGC CACAGTTTGGCCTGATGAAGAGG
THBS2 NM_003247 2361 CAAGACTGGC 2362 CAGCGTAGGT 2363 TGAGTCTGCCAT 2364 CAAGACTGGCTACATCAGAGTCTTAGTGCATGAAGGAAAACAG
TACATCAGAG TTGGTCATAG GACCTGTTTTCC GTCATGGCAGACTCAGGACCTATCTATGACCAAACCTACGCTG
TCTTAGTG ATAGG TTCAT
THY1 NM_006288 2365 GGACAAGACC 2366 TTGGAGGCTG 2367 CAAGCTCCCAAG 2368 GGACAAGACCCTCTCAGGCTGTCCCAAGCTCCCAAGAGCTTC
CTCTCAGGCT TGGGTCAG AGCTTCCAGAGC CAGAGCTCTGACCCACAGCCTCCAA
TIAM1 NM_003253 2369 GTCCCTGGCT 2370 GGGCTCCCGA 2371 TGGAGCCCTTCT 2372 GTCCCTGGCTGAAAATGGCCTGGAGCCCTTCTCCCAAGATGG
GAAAATGG AGTCTTCTA CCCAAGATGGTA TACCCTAGAAGACTTCGGGAGCCC
TIMP2 NM_003255 2373 TCACCCTCTG 2374 TGTGGTTCAG 2375 CCCTGGGACACC 2376 TCACCCTCTGTGACTTCATCGTGCCCTGGGACACCCTGAGCAC
TGACTTCATC GCTCTTCTTC CTGAGCACCA CACCCAGAAGAAGAGCCTGAACCACA
GT TG
TIMP3 NM_000362 2377 CTACCTGCCT 2378 ACCGAAATTG 2379 CCAAGAACGAGT 2380 CTACCTGCCTTGCTTTGTGACTTCCAAGAACGAGTGTCTCTGG
TGCTTTGTGA GAGAGCATGT GTCTCTGGACCG ACCGACATGCTCTCCAATTTCGGT
TK1 NM_003258 2381 GCCGGGAAGA 2382 CAGCGGCACC 2383 CAAATGGCTTCC 2384 GCCGGGAAGACCGTAATTGTGGCTGCACTGGATGGGACCTTC
CCGTAATTGT AGGTTCAG TCTGGAAGGTCC CAGAGGAAGCCATTTGGGGCCATCCTGAACCTGGTGCCGCTG
CA
TMPRSS2 NM_005656 2385 GGACAGTGTG 2386 CTCCCACGAG 2387 AAGCACTGTGCA 2388 GGACAGTGTGCACCTCAAAGACTAAGAAAGCACTGTGCATCAC
CACCTCAAAG GAAGGTCC TCACCTTGACCC CTTGACCCTGGGGACCTTCCTCGTGGGAG
TMPRSS2 DQ204772 2389 GAGGCGGAGG 2390 ACTGGTCCTC 2391 TAAGGCTTCCTG 2392 GAGGCGGAGGCGGAGGGCGAGGGGCGGGGAGCGCCGCCTG
ERG A GCGAG ACTCACAACT CCGCGCTCCA GAGCGCGGCAGGAAGCCTTATCAGTTGTGAGTGAGGACCAGT
TMPRSS2 DQ204773 2393 GAGGCGGAGG 2394 TTCCTCGGGT 2395 CCTGGAATAACC 2396 GAGGCGGAGGGCGAGGGGCGGGGAGCGCCGCCTGGAGCGC
ERG B GCGAG CTCCAAAGAT TGCCGCGC GGCAGGTTATTCCAGGATCTTTGGAGACCCGAGGAA
TNF NM_000594 2397 GGAGAAGGGT 2398 TGCCCAGACT 2399 CGCTGAGATCAA 2400 GGAGAAGGGTGACCGACTCAGCGCTGAGATCAATCGGCCCGA
GACCGACTCA CGGCAAAG TCGGCCCGACTA CTATCTCGACTTTGCCGAGTCTGGGCA
TNFRS NM_003844 2401 TGCACAGAGG 2402 TCTTCATCTG 2403 CAATGCTTCCAA 2404 TGCACAGAGGGTGTGGGTTACACCAATGCTTCCAACAATTTGT
F10A GTGTGGGTTA ATTTACAAGC CAATTTGTTTGC TTGCTTGCCTCCCATGTACAGCTTGTAAATCAGATGAAGA
C TGTACATG TTGCC
TNFRS NM_003842 2405 CTCTGAGACA 2406 CCATGAGGCC 2407 CAGACTTGGTGC 2408 CTCTGAGACAGTGCTTCGATGACTTTGCAGACTTGGTGCCCTT
F10B GTGCTTCGAT CAACTTCCT CCTTTGACTCC TGACTCCTGGGAGCCGCTCATGAGGAAGTTGGGCCTCATGG
GACT
TNFRSF18 NM_148901 2409 CAGAAGCTGC 2410 CACCCACAGG 2411 CCTTCTCCTCTG 2412 CAGAAGCTGCCAGTTCCCCGAGGAAGAGCGGGGCGAGCGAT
CAGTTCCC TCTCCCAG CCGATCGCTC CGGCAGAGGAGAAGGGGCGGCTGGGAGACCTGTGGGTG
TNFSF10 NM_003810 2413 CTTCACAGTG 2414 CATCTGCTTC 2415 AAGTACACGTAA 2416 CTTCACAGTGCTCCTGCAGTCTCTCTGTGTGGCTGTAACTTAC
CTCCTGCAGT AGCTCGTTGG GTTACAGCCACA GTGTACTTTACCAACGAGCTGAAGCAGATG
CT T CA
TNFSF11 NM_003701 2417 AACTGCATGT 2418 TGACACCCTC 2419 ACATGACCAGGG 2420 AACTGCATGTGGGCTATGGGAGGGGTTGGTCCCTGGTCATGT
GGGCTATGG TCCACTTCAG ACCAACCCCTC GCCCCTTCGCAGCTGAAGTGGAGAGGGTGTCA
TOP2A NM_001067 2421 AATCCAAGGG 2422 GTACAGATTT 2423 CATATGGACTTT 2424 AATCCAAGGGGGAGAGTGATGACTTCCATATGGACTTTGACTC
GGAGAGTGAT TGCCCGAGGA GACTCAGCTGTG AGCTGTGGCTCCTCGGGCAAAATCTGTAC
GC
TP53 NM_000546 2425 CTTTGAACCC 2426 CCCGGGACAA 2427 AAGTCCTGGGTG 2428 CTTTGAACCCTTGCTTGCAATAGGTGTGCGTCAGAAGCACCCA
TTGCTTGCAA AGCAAATG CTTCTGACGCAC GGACTTCCATTTGCTTTGTCCCGGG
A
TP63 NM_003722 2429 CCCCAAGCAG 2430 GAATCGCACA 2431 CCCGGGTCTCAC 2432 CCCCAAGCAGTGCCTCTACAGTCAGTGTGGGCTCCAGTGAGA
TGCCTCTACA GCATCAATAA TGGAGCCCA CCCGGGGTGAGCGTGTTATTGATGCTGTGCGATTC
CAC
TPD52 NM_005079 2433 GCCTGTGAGA 2434 ATGTGCTTGG 2435 TCTGCTACCCAC 2436 GCCTGTGAGATTCCTACCTTTGTTCTGCTACCCACTGCCAGAT
TTCCTACCTT ACCTCGCTT TGCCAGATGCTG GCTGCAAGCGAGGTCCAAGCACAT
TG
TPM1 NM_ 2437 TCTCTGAGCT 2438 GGCTCTAAGG 2439 TTCTCCAGCTGA 2440 TCTCTGAGCTCTGCATTTGTCTATTCTCCAGCTGACCCTGGTT
001018005 CTGCATTTGT CAGGATGCTA CCCTGGTTCTCT CTCTCTCTTAGCATCCTGCCTTAGAGCC
C C
TPM2 NM_213674 2441 AGGAGATGCA 2442 CCACCTCTTC 2443 CCAAGCACATCG 2444 AGGAGATGCAGCTGAAGGAGGCCAAGCACATCGCTGAGGATT
GCTGAAGGAG ATATTTGCGG CTGAGGATTCAG CAGACCGCAAATATGAAGAGGTGG
TPP2 NM_003291 2445 TAACCGTGGC 2446 ATGCCAACGC 2447 ATCCTGTTCAGG 2448 TAACCGTGGCATCTACCTCCGAGATCCTGTTCAGGTGGCTGCA
ATCTACCTCC CATGATCT TGGCTGCACCTT CCTTCAGATCATGGCGTTGGCAT
TPX2 NM_012112 2449 TCAGCTGTGA 2450 ACGGTCCTAG 2451 CAGGTCCCATTG 2452 TCAGCTGTGAGCTGCGGATACCGCCCGGCAATGGGACCTGCT
GCTGCGGATA GTTTGAGGTT CCGGGCG CTTAACCTCAAACCTAGGACCGT
AAGA
TRA2A NM_013293 2453 GCAAATCCAG 2454 CTTCACGAAG 2455 AACTGAGGCCAA 2456 GCAAATCCAGATCCCAACACTTGCCTTGGAGTGTTTGGCCTCA
ATCCCAACAC ATCCCTCTCT ACACTCCAAGGC GTTTGTACACAACAGAGAGGGATCTTCGTGAAG
G
TRAF3IP2 NM_147200 2457 CCTCACAGGA 2458 CTGGGGCTGG 2459 TGGATCTGCCAA 2460 CCTCACAGGAACCGAGCAGGCCTGGATCTGCCAACCATAGAC
ACCGAGCA GAATCATA CCATAGACACGG ACGGGATATGATTCCCAGCCCCAG
TRAM1 NM_014294 2461 CAAGAAAAGC 2462 ATGTCCGCGT 2463 AGTGCTGAGCCA 2464 CAAGAAAAGCACCAAGAGCCCCCCAGTGCTGAGCCACGAATT
ACCAAGAGCC GATTCTGC CGAATTCGTCC CGTCCTGCAGAATCACGCGGACAT
TRAP1 NM_016292 2465 TTACCAGTGG 2466 TGTCCCGGTT 2467 TTCGGCGATTTC 2468 TTACCAGTGGCTTTCAGATGGTTCTGGAGTGTTTGAAATCGCC
CTTTCAGATG CTAACTCCC AAACACTCCAGA GAAGCTTCGGGAGTTAGAACCGGGACA
G
TRIM14 NM_033220 2469 CATTCGCCTT 2470 CAAGGTACCT 2471 AACTGCCAGCTC 2472 CATTCGCCTTAAGGAAAGCATAAACTGCCAGCTCTCAGACCCT
AAGGAAAGCA GGCTTGGTG TCAGACCCTTCC TCCAGCACCAAGCCAGGTACCTTG
TRO NM_177556 2473 GCAACTGCCA 2474 TGGTGTGGAT 2475 CCACCCAAGGCC 2476 GCAACTGCCACCCATACAGCTACCACCCAAGGCCAAATTACCA
CCCATACAG ACTGGCTGTC AAATTACCAATG ATGAGACAGCCAGTATCCACACCA
TRPC6 NM_004621 2477 CGAGAGCCAG 2478 TAGCCGTAGC 2479 CTTCTCCCAGCT 2480 CGAGAGCCAGGACTATCTGCTCATGGACTCGGAGCTGGGAGA
GACTATCTGC AAGGCAGC CCGAGTCCATG AGACGGCTGCCCGCAAGCCCCGCTGCCTTGCTACGGCTA
TRPV6 NM_018646 2481 CCGTAGTCCC 2482 TCCTCACTGT 2483 ACTTTGGGGAGC 2484 CCGTAGTCCCTGCAACCTCATCTACTTTGGGGAGCACCCTTTG
TGCAACCTC TCACACAGGC ACCCTTTGTCCT TCCTTTGCTGCCTGTGTGAACAGTGAGGA
TSTA3 NM_003313 2485 CAATTTGGAC 2486 CACCTCAAAG 2487 AACGTGCACATG 2488 CAATTTGGACTTCTGGAGGAAAAACGTGCACATGAACGACAAC
TTCTGGAGGA GCCGAGTG AACGACAACGTC GTCCTGCACTCGGCCTTTGAGGTG
A
TUBB2A NM_001069 2489 CGAGGACGAG 2490 ACCATGCTTG 2491 TCTCAGATCAAT 2492 CGAGGACGAGGCTTAAAAACTTCTCAGATCAATCGTGCATCCT
GCTTAAAAAC AGGACAACAG CGTGCATCCTTA TAGTGAACTTCTGTTGTCCTCAAGCATGGT
GTGAA
TYMP NM_001953 2493 CTATATGCAG 2494 CCACGAGTTT 2495 ACAGCCTGCCAC 2496 CTATATGCAGCCAGAGATGTGACAGCCACCGTGGACAGCCTG
CCAGAGATGT CTTACTGAGA TCATCACAGCC CCACTCATCACAGCCTCCATTCTCAGTAAGAAACTCGTGG
GACA ATGG
TYMS NM_001071 2497 GCCTCGGTGT 2498 CGTGATGTGC 2499 CATCGCCAGCTA 2500 GCCTCGGTGTGCCTTTCAACATCGCCAGCTACGCCCTGCTCAC
GCCTTTCA GCAATCATG CGCCCTGCTC GTACATGATTGCGCACATCACG
UAP1 NM_003115 2501 CTGGAGACGG 2502 GCCAAGCTTT 2503 TACCTGTAAACC 2504 CTGGAGACGGTCGTAGCTGCGGTCGCGCCGAGAAAGGTTTAC
TCGTAGCTG GTAGAAATAG TTTCTCGGCGCG AGGTACATACATTACACCCCTATTTCTACAAAGCTTGGC
GG
UBE2C NM_007019 2505 TGTCTGGCGA 2506 ATGGTCCCTA 2507 TCTGCCTTCCCT 2508 TGTCTGGCGATAAAGGGATTTCTGCCTTCCCTGAATCAGACAA
TAAAGGGATT CCCATTTGAA GAATCAGACAAC CCTTTTCAAATGGGTAGGGACCAT
C
UBE2G1 NM_003342 2509 TGACACTGAA 2510 AAGCAGAGAG 2511 TTGTCCCACCAG 2512 TGACACTGAACGAGGTGGCTTTTGTCCCACCAGTGCCTCATCA
CGAGGTGGC GAATCGCCT TGCCTCATCAGT GTGTGAGGCGATTCCTCTCTGCTT
UBE2T NM_014176 2513 TGTTCTCAAA 2514 AGAGGTCAAC 2515 AGGTGCTTGGAG 2516 TGTTCTCAAATTGCCACCAAAAGGTGCTTGGAGACCATCCCTC
TTGCCACCAA ACAGTTGCGA ACCATCCCTCAA AACATCGCAACTGTGTTGACCTCT
UGDH NM_003359 2517 GAAACTCCAG 2518 CTCTGGGAAC 2519 TATACAGCACAC 2520 GAAACTCCAGAGGGCCAGAGAGCTGTGCAGGCCCTGTGTGCT
AGGGCCAGA CCAGTGCTC AGGGCCTGCACA GTATATGAGCACTGGGTTCCCAGAG
UGT2B15 NM_001076 2521 AAGCCTGAAG 2522 CCTCCATTTA 2523 AAAGATGGGACT 2524 AAGCCTGAAGTGGAATGACTGAAAGATGGGACTCCTCCTTTAT
TGGAATGACT AAACCCTCCA CCTCCTTTATTT TTCAGCATGGAGGGTTTTAAATGGAGG
G CAGCA
UGT2B17 NM_001077 2525 TTGAGTTTGT 2526 TCCAGGTGAG 2527 ACCCGAAGGTGC 2528 TTGAGTTTGTCATGCGCCATAAAGGAGCCAAGCACCTTCGGGT
CATGCGCC GTTGTGGG TTGGCTCCTTTA CGCAGCCCACAACCTCACCTGGA
UHRF1 NM_013282 2529 CTACAGGGGC 2530 GGTGTCATTC 2531 CGGCCATACCCT 2532 CTACAGGGGCAAACAGATGGAGGACGGCCATACCCTCTTCGA
AAACAGATGG AGGCGGAC CTTCGACTACGA CTACGAGGTCCGCCTGAATGACACC
UTP23 NM_032334 2533 GATTGCACAA 2534 GGAAAGCAGA 2535 TCGAAATTGTCC 2536 GATTGCACAAAAATGCCAAGTTCGAAATTGTCCTCATTTCAAG
AAATGCCAAG CATTCTGATC TCATTTCAAGAA AATGCAGTGAGTGGATCAGAATGTCTGCTTTCC
C TGCA
VCAM1 NM_001078 2537 TGGCTTCAGG 2538 TGCTGTCGTG 2539 CAGGCACACACA 2540 TGGCTTCAGGAGCTGAATACCCTCCCAGGCACACACAGGTGG
AGCTGAATAC ATGAGAAAAT GGTGGGACACAA GACACAAATAAGGGTTTTGGAACCACTATTTTCTCATCACGAC
C AGTG AT AGCA
VCL NM_003373 2541 GATACCACAA 2542 TCCCTGTTAG 2543 AGTGGCAGCCAC 2544 GATACCACAACTCCCATCAAGCTGTTGGCAGTGGCAGCCACG
CTCCCATCAA GCGCATCAG GGCGCC GCGCCTCCTGATGCGCCTAACAGGGA
GCT
VCPIP1 NM_025054 2545 TTTCTCCCAG 2546 TGAATAGGGA 2547 TGGTCCATCCTC 2548 TTTCTCCCAGTACCATTCGTGATGGTCCATCCTCTGCACCTGC
TACCATTCGT GCCTTGGTAG TGCACCTGCTAC TACACCTACCAAGGCTCCCTATTCA
G G
VDR NM_000376 2549 CCTCTCCTTC 2550 TCATTGCCAA 2551 CAGCATGAAGCT 2552 CCTCTCCTTCCAGCCTGAGTGCAGCATGAAGCTAACGCCCCTT
CAGCCTGAGT ACACTTCGAG AACGCCCCTTGT GTGCTCGAAGTGTTTGGCAATGA
VEGFA NM_003376 2553 CTGCTGTCTT 2554 GCAGCCTGGG 2555 TTGCCTTGCTGC 2556 CTGCTGTCTTGGGTGCATTGGAGCCTTGCCTTGCTGCTCTACC
GGGTGCATTG ACCACTTG TCTACCTCCACC TCCACCATGCCAAGTGGTCCCAGGCTGC
A
VEGFB NM_003377 2557 TGACGATGGC 2558 GGTACCGGAT 2559 CTGGGCAGCACC 2560 TGACGATGGCCTGGAGTGTGTGCCCACTGGGCAGCACCAAGT
CTGGAGTGT CATGAGGATC AAGTCCGGA CCGGATGCAGATCCTCATGATCCGGTACC
TG
VEGFC NM_005429 2561 CCTCAGCAAG 2562 AAGTGTGATT 2563 CCTCTCTCTCAA 2564 CCTCAGCAAGACGTTATTTGAAATTACAGTGCCTCTCTCTCAA
ACGTTATTTG GGCAAAACTG GGCCCCAAACCA GGCCCCAAACCAGTAACAATCAGTTTTGCCAATCACACTT
AAATT ATTG GT
VIM NM_003380 2565 TGCCCTTAAA 2566 GCTTCAACGG 2567 ATTTCACGCATC 2568 TGCCCTTAAAGGAACCAATGAGTCCCTGGAACGCCAGATGCG
GGAACCAATG CAAAGTTCTC TGGCGTTCCA TGAAATGGAAGAGAACTTTGCCGTTGAAGC
A TT
VTI1B NM_006370 2569 ACGTTATGCA 2570 CCGATGGAGT 2571 CGAAACCCCATG 2572 ACGTTATGCACCCCTGTCTTTCCGAAACCCCATGATGTCTAAG
CCCCTGTCTT TTAGCAAGGT ATGTCTAAGCTT CTTCGAAACTACCGGAAGGACCTTGCTAAACTCCATCGG
CG
WDR19 NM_025132 2573 GAGTGGCCCA 2574 GATGCTTGAG 2575 CCCCTCGACGTA 2576 GAGTGGCCCAGATGTCCATAAGAATGGGAGACATACGTCGAG
GATGTCCATA GGCTTGGTT TGTCTCCCATTC GGGTTAACCAAGCCCTCAAGCATC
WFDC1 NM_021197 2577 ACCCCTGCTC 2578 ATACCTTCGG 2579 CTATGAGTGCCA 2580 ACCCCTGCTCTGTCCCTCGGGCTATGAGTGCCACATCCTGAG
TGTCCCTC CCACGTCAC CATCCTGAGCCC CCCAGGTGACGTGGCCGAAGGTAT
WISP1 NM_003882 2581 AGAGGCATCC 2582 CAAACTCCAC 2583 CGGGCTGCATCA 2584 AGAGGCATCCATGAACTTCACACTTGCGGGCTGCATCAGCACA
ATGAACTTCA AGTACTTGGG GCACACGC CGCTCCTATCAACCCAAGTACTGTGGAGTTTG
CA TTGA
WNT5A NM_003392 2585 GTATCAGGAC 2586 TGTCGGAATT 2587 TTGATGCCTGTC 2588 GTATCAGGACCACATGCAGTACATCGGAGAAGGCGCGAAGAC
CACATGCAGT GATACTGGCA TTCGCGCCTTCT AGGCATCAAAGAATGCCAGTATCAATTCCGACA
ACATC TT
WWOX NM_016373 2589 ATCGCAGCTG 2590 AGCTCCCTGT 2591 CTGCTGTTTACC 2592 ATCGCAGCTGGTGGGTGTACACACTGCTGTTTACCTTGGCGAG
GTGGGTGTAC TGCATGGACT TTGGCGAGGCCT GCCTTTCACCAAGTCCATGCAACAGGGAGCT
T TTC
XIAP NM_001167 2593 GCAGTTGGAA 2594 TGCGTGGCAC 2595 TCCCCAAATTGC 2596 GCAGTTGGAAGACACAGGAAAGTATCCCCAAATTGCAGATTTA
GACACAGGAA TATTTTCAAG AGATTTATCAAC TCAACGGCTTTTATCTTGAAAATAGTGCCACGCA
AGT A GGC
XRCC5 NM_021141 2597 AGCCCACTTC 2598 AGCAGGATTC 2599 TCTGGCTGAAGG 2600 AGCCCACTTCAGCGTCTCCAGTCTGGCTGAAGGCAGTGTCAC
AGCGTCTC ACACTTCCAA CAGTGTCACCTC CTCTGTTGGAAGTGTGAATCCTGCT
C
YY1 NM_003403 2601 ACCCGGGCAA 2602 GACCGAGAAC 2603 TTGATCTGCACC 2604 ACCCGGGCAACAAGAAGTGGGAGCAGAAGCAGGTGCAGATCA
CAAGAAGT TCGCCCTC TGCTTCTGCTCC AGACCCTGGAGGGCGAGTTCTCGGTC
ZFHX3 NM_006885 2605 CTGTGGAGCC 2606 GGAGCAGGGT 2607 ACCTGGCCCAAC 2608 CTGTGGAGCCTCTGCCTGCGGACCTGGCCCAACTCTACCAGC
TCTGCCTG TGGATTGAG TCTACCAGCATC ATCAGCTCAATCCAACCCTGCTCC
ZFP36 NM_003407 2609 CATTAACCCA 2610 CCCCCACCAT 2611 CAGGTCCCCAAG 2612 CATTAACCCACTCCCCTGACCTCACGCTGGGGCAGGTCCCCA
CTCCCCTGA CATGAATACT TGTGCAAGCTC AGTGTGCAAGCTCAGTATTCATGATGGTGGGGG
ZMYND8 NM_183047 2613 GGTCTGGGCC 2614 TGCCCGTCTT 2615 CTTTTGCAGGCC 2616 GGTCTGGGCCAAACTGAAGGGGTTTCCATTCTGGCCTGCAAAA
AAACTGAAG TATCCCTTAG AGAATGGAAACC GCTCTAAGGGATAAAGACGGGCA
ZNF3 NM_017715 2617 CGAAGGGACT 2618 GCAGGAGGTC 2619 AGGAGGTTCCAC 2620 CGAAGGGACTCTGCTCCAGTGAACTGGCGAGTGTGGAACCTC
CTGCTCCA CTCAGAAGG ACTCGCCAGTTC CTGACACCTTCTGAGGACCTCCTGC
ZNF827 NM_178835 2621 TGCCTGAGGA 2622 GAGGTGGCGG 2623 CCCGCCTTCAGA 2624 TGCCTGAGGACCCTCTACCGCCCCCGCCTTCAGAGAAGAAAC
CCCTCTACC AGTGACTTT GAAGAAACCAGA CAGAAAAAGTCACTCCGCCACCTC
ZWINT NM_007057 2625 TAGAGGCCAT 2626 TCCGTTTCCT 2627 ACCAAGGCCCTG 2628 TAGAGGCCATCAAAATTGGCCTCACCAAGGCCCTGACTCAGAT
CAAAATTGGC CTGGGCTT ACTCAGATGGAG GGAGGAAGCCCAGAGGAAACGGA
TABLE B
SEQ
ID
microRNA Sequence NO
hsa-miR-1 UGGAAUGUAAAGAAGUAUGUAU 2629
hsa-miR-103 GCAGCAUUGUACAGGGCUAUGA 2630
hsa-miR-106b UAAAGUGCUGACAGUGCAGAU 2631
hsa-miR-10a UACCCUGUAGAUCCGAAUUUGUG 2632
hsa-miR-133a UUUGGUCCCCUUCAACCAGCUG 2633
hsa-miR-141 UAACACUGUCUGGUAAAGAUGG 2634
hsa-miR-145 GUCCAGUUUUCCCAGGAAUCCCU 2635
hsa-miR-146b-5p UGAGAACUGAAUUCCAUAGGCU 2636
hsa-miR-150 UCUCCCAACCCUUGUACCAGUG 2637
hsa-miR-152 UCAGUGCAUGACAGAACUUGG 2638
hsa-miR-155 UUAAUGCUAAUCGUGAUAGGGGU 2639
hsa-miR-182 UUUGGCAAUGGUAGAACUCACACU 2640
hsa-miR-191 CAACGGAAUCCCAAAAGCAGCUG 2641
hsa-miR-19b UGUAAACAUCCUCGACUGGAAG 2642
hsa-miR-200c UAAUACUGCCGGGUAAUGAUGGA 2643
hsa-miR-205 UCCUUCAUUCCACCGGAGUCUG 2644
hsa-miR-206 UGGAAUGUAAGGAAGUGUGUGG 2645
hsa-miR-21 UAGCUUAUCAGACUGAUGUUGA 2646
hsa-miR-210 CUGUGCGUGUGACAGCGGCUGA 2647
hsa-miR-22 AAGCUGCCAGUUGAAGAACUGU 2648
hsa-miR-222 AGCUACAUCUGGCUACUGGGU 2649
hsa-miR-26a UUCAAGUAAUCCAGGAUAGGCU 2650
hsa-miR-27a UUCACAGUGGCUAAGUUCCGC 2651
hsa-miR-27b UUCACAGUGGCUAAGUUCUGC 2652
hsa-miR-29b UAGCACCAUUUGAAAUCAGUGUU 2653
hsa-miR-30a CUUUCAGUCGGAUGUUUGCAGC 2654
hsa-miR-30e-5p CUUUCAGUCGGAUGUUUACAGC 2655
hsa-miR-31 AGGCAAGAUGCUGGCAUAGCU 2656
hsa-miR-331 GCCCCUGGGCCUAUCCUAGAA 2657
hsa-miR-425 AAUGACACGAUCACUCCCGUUGA 2658
hsa-miR-449a UGGCAGUGUAUUGUUAGCUGGU 2659
hsa-miR-486-5p UCCUGUACUGAGCUGCCCCGAG 2660
hsa-miR-92a UAUUGCACUUGUCCCGGCCUGU 2661
hsa-miR-93 CAAAGUGCUGUUCGUGCAGGUAG 2662
hsa-miR-99a AACCCGUAGAUCCGAUCUUGUG 2663
