This application 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: NO: 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 N0 M0 G1; Stage II: (T1a N0M0G2-4) or (T1b, c, T1, T2, N0 M0 Any G); Stage III: T3 N0 M0 Any G; Stage 1V: (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 Andrés 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 MasterPure™ 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, Calif., 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 (3-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, CW. 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 For patients whose prostatectomy
primary Gleason pattern is also primary Gleason pattern is not
the highest Gleason pattern the highest Gleason pattern
Specimen 1 (A1) = primary Specimen 1 (B1) = highest
Gleason pattern Gleason pattern
Select and mark largest focus Select highest Gleason pattern tissue
(greatest cross-sectional area) of from spatially distinct area from
primary Gleason pattern tissue. specimen B2, if possible. Invasive
Invasive cancer area ≧5.0 mm. 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 Specimen 2 (B2) = primary
Gleason pattern Gleason pattern
Select and mark secondary Gleason Select largest focus (greatest
pattern tissue from spatially cross-sectional area) of primary
distinct area from specimen A1. Gleason pattern tissue. Invasive
Invasive cancer area ≧5.0 mm. 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
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)
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
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)
Primary Highest
Pattern 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
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
Primary Highest Primary Highest
Pattern Pattern Pattern Pattern
Official p- p- p- p-
Symbol HR value HR value HR value HR 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
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
Primary Highest Primary Highest
Pattern Pattern Pattern Pattern
Official p- p- p- p-
Symbol HR value HR value HR value HR 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
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
Primary Highest Primary Highest
Pattern Pattern Pattern Pattern
Official p- p- p- p-
Symbol HR value HR value HR value HR 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
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 bRFI
Official Primary Pattern Highest Pattern Primary Pattern Highest Pattern
Symbol HR p-value HR p-value HR p-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
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 bRFI
Official Primary Pattern Highest Pattern Primary Pattern Highest Pattern
Symbol HR p-value HR p-value HR p-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
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 bRFI
Official Primary Pattern Highest Pattern Primary Pattern Highest Pattern
Symbol HR p-value HR p-value HR p-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
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)
Primary Highest
Pattern 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
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)
Primary Highest
Pattern 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
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)
Primary Highest
Pattern 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
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)
Primary Highest
Pattern 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
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
Official Symbol p-value Odds Ratio
ABCC8 <.001 1.86
ALDH18A1 0.005 1.49
ALKBH3 0.043 1.30
ALOX5 <.001 1.66
AMPD3 <.001 3.92
APEX1 <.001 2.00
ARHGDIB <.001 1.87
ASAP2 0.019 1.48
ATXN1 0.013 1.41
BMPR1B <.001 2.37
CACNA1D <.001 9.01
CADPS 0.015 1.39
CD276 0.003 2.25
CDH1 0.016 1.37
CDH7 <.001 2.22
CDK7 0.025 1.43
COL9A2 <.001 2.58
CRISP3 <.001 2.60
CTNND1 0.033 1.48
ECE1 <.001 2.22
EIF5 0.023 1.34
EPHB4 0.005 1.51
ERG <.001 14.5
FAM171B 0.047 1.32
FAM73A 0.008 1.45
FASN 0.004 1.50
GNPTAB <.001 1.60
GPS1 0.006 1.45
GRB7 0.023 1.38
HDAC1 <.001 4.95
HGD <.001 1.64
HIP1 <.001 1.90
HNF1B <.001 3.55
HSPA8 0.041 1.32
IGF1R 0.001 1.73
ILF3 <.001 1.91
IMMT 0.025 1.36
ITPR1 <.001 2.72
ITPR3 <.001 5.91
JAG1 0.007 1.42
KCNN2 <.001 2.80
KHDRBS3 <.001 2.63
KIAA0247 0.019 1.38
KLK11 <.001 1.98
LAMC1 0.008 1.56
LAMC2 <.001 3.30
LOX 0.009 1.41
LRP1 0.044 1.30
MAP3K5 <.001 2.06
MAP7 <.001 2.74
MSH2 0.005 1.59
MSH3 0.006 1.45
MUC1 0.012 1.42
MYO6 <.001 3.79
NCOR2 0.001 1.62
NDRG1 <.001 6.77
NETO2 <.001 2.63
ODC1 <.001 1.98
OR51E1 <.001 2.24
PDE9A <.001 2.21
PEX10 <.001 3.41
PGK1 0.022 1.33
PLA2G7 <.001 5.51
PPP3CA 0.047 1.38
PSCA 0.013 1.43
PSMD13 0.004 1.51
PTCH1 0.022 1.38
PTK2 0.014 1.38
PTK6 <.001 2.29
PTK7 <.001 2.45
PTPRK <.001 1.80
RAB30 0.001 1.60
REG4 0.018 1.58
RELA 0.001 1.62
RFX1 0.020 1.43
RGS10 <.001 1.71
SCUBE2 0.009 1.48
SEPT9 <.001 3.91
SH3RF2 0.004 1.48
SH3YL1 <.001 1.87
SHH <.001 2.45
SIM2 <.001 1.74
SIPA1L1 0.021 1.35
SLC22A3 <.001 1.63
SLC44A1 <.001 1.65
SPINT1 0.017 1.39
TFDP1 0.005 1.75
TMPRSS2ERGA 0.002 14E5
TMPRSS2ERGB <.001 1.97
TRIM14 <.001 1.65
TSTA3 0.018 1.38
UAP1 0.046 1.39
UBE2G1 0.001 1.66
UGDH <.001 2.22
XRCC5 <.001 1.66
ZMYND8 <.001 2.19
TABLE 9B
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)
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
IL1A 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
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)
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
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)
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
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 Pattern Primary Pattern Highest 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
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)
Official Symbol HR p-value
AKR1C3 1.476 0.016
ANLN 1.517 0.006
APOC1 1.285 0.016
APOE 1.490 0.024
ASPN 3.055 <.001
ATP5E 1.788 0.012
AURKB 1.439 0.008
BGN 2.640 <.001
BIRC5 1.611 <.001
BMP6 1.490 0.021
BRCA1 1.418 0.036
CCNB1 1.497 0.021
CD276 1.668 0.005
CDC20 1.730 <.001
CDH11 1.565 0.017
CDH7 1.553 0.007
CDKN2B 1.751 0.003
CDKN2C 1.993 0.013
CDKN3 1.404 0.008
CENPF 2.031 <.001
CHAF1A 1.376 0.011
CKS2 1.499 0.031
COL1A1 2.574 <.001
COL1A2 1.607 0.011
COL3A1 2.382 <.001
COL4A1 1.970 <.001
COL5A2 1.938 0.002
COL8A1 2.245 <.001
CTHRC1 2.085 <.001
CXCR4 1.783 0.007
DDIT4 1.535 0.030
DYNLL1 1.719 0.001
F2R 2.169 <.001
FAM171B 1.430 0.044
FAP 1.993 0.002
FCGR3A 2.099 <.001
FN1 1.537 0.024
GPR68 1.520 0.018
GREM1 1.942 <.001
IFI30 1.482 0.048
IGFBP3 1.513 0.027
INHBA 3.060 <.001
KIF4A 1.355 0.001
KLK14 1.187 0.004
LAPTM5 1.613 0.006
LTBP2 2.018 <.001
MMP11 1.869 <.001
MYBL2 1.737 0.013
NEK2 1.445 0.028
NOX4 2.049 <.001
OLFML2B 1.497 0.023
PLK1 1.603 0.006
POSTN 2.585 <.001
PPFIA3 1.502 0.012
PTK6 1.527 0.009
PTTG1 1.382 0.029
RAD51 1.304 0.031
RGS7 1.251 <.001
RRM2 1.515 <.001
SAT1 1.607 0.004
SDC1 1.710 0.007
SESN3 1.399 0.045
SFRP4 2.384 <.001
SHMT2 1.949 0.003
SPARC 2.249 <.001
STMN1 1.748 0.021
SULF1 1.803 0.004
THBS2 2.576 <.001
THY1 1.908 0.001
TK1 1.394 0.004
TOP2A 2.119 <.001
TPX2 2.074 0.042
UBE2C 1.598 <.001
UGT2B15 1.363 0.016
UHRF1 1.642 0.001
ZWINT 1.570 0.010
TABLE 12B
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)
Official Symbol HR p-value
AAMP 0.649 0.040
ABCA5 0.777 0.015
ABCG2 0.715 0.037
ACOX2 0.673 0.016
ADH5 0.522 <.001
ALDH1A2 0.561 <.001
AMACR 0.693 0.029
AMPD3 0.750 0.049
ANPEP 0.531 <.001
ATXN1 0.640 0.011
AXIN2 0.657 0.002
AZGP1 0.617 <.001
BDKRB1 0.553 0.032
BIN1 0.658 <.001
BTRC 0.716 0.011
C7 0.531 <.001
CADM1 0.646 0.015
CASP7 0.538 0.029
CCNH 0.674 0.001
CD164 0.606 <.001
CD44 0.687 0.016
CDK3 0.733 0.039
CHN1 0.653 0.014
COL6A1 0.681 0.015
CSF1 0.675 0.019
CSRP1 0.711 0.007
CXCL12 0.650 0.015
CYP3A5 0.507 <.001
CYR61 0.569 0.007
DLGAP1 0.654 0.004
DNM3 0.692 0.010
DPP4 0.544 <.001
DPT 0.543 <.001
DUSP1 0.660 0.050
DUSP6 0.699 0.033
EGR1 0.490 <.001
EGR3 0.561 <.001
EIF5 0.720 0.035
ERBB3 0.739 0.042
FAAH 0.636 0.010
FAM107A 0.541 <.001
FAM13C 0.526 <.001
FAS 0.689 0.030
FGF10 0.657 0.024
FKBP5 0.699 0.040
FLNC 0.742 0.036
FOS 0.556 0.005
FOXQ1 0.666 0.007
GADD45B 0.554 0.002
GDF15 0.659 0.009
GHR 0.683 0.027
GPM6B 0.666 0.005
GSN 0.646 0.006
GSTM1 0.672 0.006
GSTM2 0.514 <.001
HGD 0.771 0.039
HIRIP3 0.730 0.013
HK1 0.778 0.048
HLF 0.581 <.001
HNF1B 0.643 0.013
HSD17B10 0.742 0.029
IER3 0.717 0.049
IGF1 0.612 <.001
IGFBP6 0.578 0.003
IL2 0.528 0.010
IL6ST 0.574 <.001
IL8 0.540 0.001
ING5 0.688 0.015
ITGA6 0.710 0.005
ITGA7 0.676 0.033
JUN 0.506 0.001
KIT 0.628 0.047
KLK1 0.523 0.002
KLK2 0.581 <.001
KLK3 0.676 <.001
KRT15 0.684 0.005
KRT18 0.536 <.001
KRT5 0.673 0.004
KRT8 0.613 0.006
LAMB3 0.740 0.027
LGALS3 0.678 0.007
MGST1 0.640 0.002
MPPED2 0.629 <.001
MTSS1 0.705 0.041
MYBPC1 0.534 <.001
NCAPD3 0.519 <.001
NFAT5 0.536 <.001
NRG1 0.467 0.007
OLFML3 0.646 0.001
OMD 0.630 0.006
OR51E2 0.762 0.017
PAGE4 0.518 <.001
PCA3 0.581 <.001
PGF 0.705 0.038
PPAP2B 0.568 <.001
PPP1R12A 0.694 0.017
PRIMA1 0.678 0.014
PRKCA 0.632 0.001
PRKCB 0.692 0.028
PROM1 0.393 0.017
PTEN 0.689 0.002
PTGS2 0.611 0.004
PTH1R 0.629 0.031
RAB27A 0.721 0.046
RND3 0.678 0.029
RNF114 0.714 0.035
SDHC 0.590 <.001
SERPINA3 0.710 0.050
SH3RF2 0.570 0.005
SLC22A3 0.517 <.001
SMAD4 0.528 <.001
SMO 0.751 0.026
SRC 0.667 0.004
SRD5A2 0.488 <.001
STAT5B 0.700 0.040
SVIL 0.694 0.024
TFF3 0.701 0.045
TGFB1I1 0.670 0.029
TGFB2 0.646 0.010
TNFRSF10B 0.685 0.014
TNFSF10 0.532 <.001
TPM2 0.623 0.005
TRO 0.767 0.049
TUBB2A 0.613 0.003
VEGFB 0.780 0.034
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
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))
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
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))
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
Deaths Due to
Patients Clinical Recurrences Prostate Cancer
Primary Gleason 416 106 36
Pattern Tumor Tissue
Highest Gleason 405 102 36
Pattern Tumor Tissue
Normal Adjacent 364 81 29
Tissue
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.
c RM: 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 Predictive of
Total Number of Clinical Recurrence at False
Tier MicroRNA-Gene 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 SEQ SEQ SEQ
Official Accession ID Forward ID Reverse ID ID
Symbol: Number: NO Primer Sequence: NO Primer Sequence: NO Probe Sequence: NO Amplicon Sequence:
AAMP NM_001087 1 GTGTGGCAGGTGGAC 2 CTCCATCCACTCCAGG 3 CGCTTCAAAGGACC 4 GTGTGGCAGGTGGACACTAAGGAGGAGGTCTGGTCCTTT
ACTAA TCTC AGACCTCCTC GAAGCGGGAGACCTGGAGTGGATGGAG
ABCA5 NM_172232 5 GGTATGGATCCCAAA 6 CAGCCCGCTTTCTGTT 7 CACATGTGGCAGAG 8 GGTATGGATCCCAAAGCCAAACAGCACATGTGGCGAGCA
GCCA TTTA CAATTCGAACT ATTCGAACTGCATTTAAAAACAGAAAGCGGGCT
ABCD1 NM_000927 9 AAACACCACTGGAGC 10 CAAGCCTGGAACCTAT 11 CAAGCCTGGAACCT 12 AAACACCACTGGAGCATTGACTACCAGGCTCGCCAATGA
ATTGA AGCC ATAGCC TGCTGCTCAAGTTAAAGGGGCTATAGGTTCCAG
ABCC1 NM_004996 13 TCATGGTGCCCGTCA 14 CGATTGTCTTTGCTCT 15 ACCTGATACGTCTT 16 TCATGGTGCCCGTCAATGCTGTGATGGCGATGAAGACCA
ATG TCATGTG GGTCTTCATCGCCA AGACGTATCAGGTGGCCCACATGAAGAGCAAAG
T
ABCC3 NM_003786 17 TCATCCTGGCGATCT 18 CCGTTGAGTGGAATCA 19 TCTGTCCTGGCTGG 20 TCATCCTGGCGATCTACTTCCTCTGGCAGAACCTAGGTC
ACTTCCT GCAA AGTCGCTTTCAT CCTCTGTCCTGGCTGGAGTCGCTTTCATGGTCTTGCTGA
TTCCACTCAACGG
ABCC4 NM_005845 21 AGCGCCTGGAATCTA 22 AGAGCCCCTGGAGAGA 23 CGGAGTCCAGTGTT 24 AGCGCCTGGAATCTACAACTCGGAGTCCAGTGTTTTCCC
CAACT AGAT TTCCCACTTA ACTTATCATCTTCTCTCCAGGGGCTCT
ABCC8 NM_000351 25 CGTCTGTCACTGTGG 26 TGATCCGGTTTAGCAG 27 AGTCTCTTGGCCAC 28 CGTCTGTCACTGTGGAGTGGACAGGGCTGAAGGTGGCCA
AGTGG GC CTTCAGCCCT AGAGACTGCACCGCAGCCTGCTAAACCGGATCA
ABCG2 NM_004827 29 GGTCTCAACGGCATC 30 CTTGGATCTTTCCTTG 31 ACGAAGATTTGCCT 32 GGTCTCAACGCCATCCTGGGACCCACAGGTGGAGGCAAA
CTG CAGC CCACCTGTGG TCTTCGTTATTAGATGTCTTAGCTGCAAGGAAAG
ABHD2 NM_007011 33 GTAGTGGGTCTGCAT 34 TGAGGGTTGGCACTCA 35 CAGGTGGCTCCTTT 36 GTAGTGGGTCTGCATGGATGTTTCAGGGATCAAAGGAGC
GGATGT GG GATCCCTGA CACCTGGGCGCCTGAGTGCCAACCCTCA
ACE NM_000789 37 CCGCTGTACGAGGAT 38 CCGTGTCTGTGAAGCC 39 TGCCCTCAGCAATG 40 CCGCTGTACGAGGATTTCACTGCCCTCAGCAATGAAGCC
TTCA GT AAGCCTACAA TACAAGCAGGACGGCTTCACAGACACGG
ACOX2 NM_003500 41 ATGGAGGTGCCCAGA 42 ACTCCGGGTAACTGTG 43 TGCTCTCAACTTTC 44 ATGGAGGTGCCCAGAACACTGCACTCCGCAGGAAAGTTG
ACAC GATG CTGCGGAGTG AGAGCATCATCCACAGTTACCCGGAGT
ACTR2 NM_005722 45 ATCCGCATTGAAGAC 46 ATCCGCTAGAACTGCA 47 CCCGCAGAAAGCAC 48 ATCCGCATTGAAGACCCACCCCGCAGAAAGCACATGGTA
CCA CCAC ATGGTATTCC TTCCTGGGTGGTGCAGTTCTAGCGGAT
ADAM15 NM_003815 49 GGCGGGATGTGGT 50 ATTTCTGGGCCTCCG 51 TCAGCCACAATCAC 52 GGCGGGATGTGGTAACAGAGACCAAGACTGTGGAGT
CAACTC
ADAMTS1 NM_006988 53 GGACAGGTGCAAGCT 54 ATCTACAACCTTGGGC 55 CAAGCCAAAGGCAT 56 GGACAGGTGCAAGCTCATCTGCCAAGCCAAAGGCATTGG
CATCTG TGCAA TGGCTACTTCTTCG CTACTTCTTCGTTTTGCAGCCCAAGGTTGTAGAT
ADH5 NM_000671 57 ATGCTGTCATCATT 58 CTGCTTCCTTTCCCTT 59 TGTCTGCCCATTAT 60 ATGCTGTCATCATTGTCACGGTTTGTCTGCCCATTAT
CTTCAT
AFAP1 NM_198595 61 GATGTCCATCCTT 62 CAACCCTGATGCCTG 63 CCTCCAGTGCTGTG 64 GATGTCCATCCTTGAAACAGCCTCTTCTGGGAACACA
TTCCCA
AGTR1 NM_000685 65 AGCATTGATCGAT 66 CTACAAGCATTGTGC 67 ATTGTTCACCCAAT 68 AGCATTGATCGATACCTGGCTATTGTTCACCCAATGA
GAAGTC
AGTR2 NM_000686 69 ACTGGCATAGGAA 70 ATTGACTGGGTCTCTT 71 CCACCCAGACCCCA 72 ACTGGCATAGGAAATGGTATCCAGAATGGAATTTTG
TGTAGC
AIG1 NM_016108 73 CGACGGTTCTGCC 74 TGCTCCTGCTGGGAT 75 AATCGAGATGAGGA 76 CGACGGTTCTGCCCTTTATATTAATCGAGATGAGGAC
CATCGC
AKAP1 NM_003488 77 TGTGGTTGGAGAT 78 GTCTACCCACTGGGC 79 CTCCACCAGGGACC 80 TGTGGTTGGAGATGAAGTGGTGTTGATAAACCGGTC
GGTTTA
AKR1C1 BC040210 81 GTGTGTGAAGCTG 82 CTCTGCAGGCGCATA 83 CCAAATCCCAGGAC 84 GTGTGTGAAGCTGAATGATGGTCACTTCATGCCTGTG
AGGCAT
AKR1C3 NM_003739 85 GCTTTGCCTGATGTC 86 GTCCAGTCACCGGCAT 87 TGCGTCACCATCCA 88 GCTTTGCCTGATGTCTACCAGAAGCCCTGTGTGTGGATG
TACCAGAA AGAGA CACACAGGG GTGACGCAGAGGACGTCTCTATGCCGGTGACTGG
AKT1 NM_005163 89 CGCTTCTATGGCG 90 TCCCGGTACACCACG 91 CAGCCCTGGACTAC 92 CGCTTCTATGGCGCTGAGATTGTGTCAGCCCTGGACT
CTGCAC
AKT2 NM_001626 93 TCCTGCCACCCTTC 94 GGCGGTAAATTCATC 95 CAGGTCACGTCCGA 96 TCCTGCCACCCTTCAAACCTCAGGTCACGTCCGAGGT
GGTCGA
AKT3 NM_005465 97 TTGTCTCTGCCTTGG 98 CCAGCATTAGATTCTC 99 TCACGGTACACAAT 100 TTGTCTCTGCCTTGGACTATCTACATTCCGGAAAGATTG
ACTATCTACA CAACTTGA CTTTCCGGA TGTACCGTGATCTCAAGTTGGAGAATCTAATGCTG
ALCAM NM_001627 101 GAGGAATATGGAA 102 GTGGCGGAGATCAAG 103 CCAGTTCCTGCCGT 104 GAGGAATATGGAATCCAAGGGGGCCAGTTCCTGCCG
CTGCTC
ALDH18A1 NM_002860 105 GATGCAGCTGGAACC 106 CTCCAGCTCAGTGGGG 107 CCTGAAACTTGCAT 108 GATGCAGCTGGAACCCAAGCTGCAGCAGGAGATGCAAGT
CAA AA CTCCTGCTGC TTCAGGATGTTCCCCACTGAGCTGGAG
ALDH1A NM_170696 109 CACGTCTGTCCCT 110 GACCGTGGCTCAACT 111 TCTCTGTAGGGCCC 112 CACGTCTGTCCCTCTCTGCTTTCTCTGTAGGGCCCAG
AGCTCT
ALKBH3 NM_139178 113 TCGCTTAGTCTGC 114 TCTGAGCCCCAGTTTT 115 TAAACAGGGCAGTC 116 TCGCTTAGTCTGCACCTCAACCGTGCGGAAAGTGACT
ACTTTC
ALOX12 NM_000697 117 AGTTCCTCAATGG 118 AGCACTAGCCTGGAG 119 CATGCTGTTGAGAC 120 AGTTCCTCAATGGTGCCAACCCCATGCTGTTGAGACG
GCTCGA
ALOX5 NM_000698 121 GAGCTGCAGGACT 122 GAAGCCTGAGGACTT 123 CCGCATGCCGTACA 124 GAGCTGCAGGACTTCGTGAACGATGTCTACGTGTAC
CGTAGA
AMACR NM_203382 125 GTCTCTGGGCTGTCA 126 TGGGTATAAGATCCAG 127 TCCATGTGTTTGAT 128 GTCTCTGGGCTGTCAGCTTTCCTTTCTCCATGTGTTTGA
GCTTT AACTTGC TTCTCCTCAGGC TTTCTCCTCAGGCTGGTAGCAAGTTCTGGATCTTA
AMPD3 NM_000480 129 TGGTTCATCCAGCAC 130 CATAAATCCGGGGCAC 131 TACTCTCCCAACAT 132 TGGTTCATCCAGCACAAGGTCTACTCTCCCAACATGCGC
AAGG CT GCGCTGGATC TGGATCATCCAGGTGCCCCGGATTTATG
ANGPT2 NM_001147 133 CCGTGAAAGCTGC 134 TTGCAGTGGGAAGAA 135 AAGCTGACACAGCC 136 CCGTGAAAGCTGCTCTGTAAAAGCTGACACAGCCCT
CTCCCA
ANLN NM_018685 137 TGAAAGTCCAAAA 138 CAGAACCAAGGCTAT 139 CCAAAGAACTCGTG 140 TGAAAGTCCAAAACCAGGAAAATTCCAAAGAACTCG
TCCCTC
ANPEP NM_001150 141 CCACCTTGGACCAAA 142 TCTCAGCGTCACCTGG 143 CTCCCCAACACGCT 144 CCACCTTGGACCAAAGTAAAGCGTGGAATCTTACCGCCT
GTAAAGC TAGGA GAAACCCG CCCCAACACGCTGAAACCCGATTCCTACCGGG
ANXA2 NM_004039 145 CAAGACACTAAGGGC 146 CGTGTCGGGCTTCAGT 147 CCACCACACAGGTA 148 CAAGACACTAAGGGCGACTACCAGAAAGCGCTGCTGTAC
GACTACCA CAT CAGCAGCGCT CTGTGTGGTGGAGATGACTGAAGCCCGACACG
APC NM_000038 149 GGACAGCAGGAAT 150 ACCCACTCGATTTGTT 151 CATTGGCTCCCCGT 152 GGACAGCAGGAATGTGTTTCTCCATACAGGTCACGG
GACCTG
APEX1 NM_001641 153 GATGAAGCCTTTC 154 AGGTCTCCACACAGC 155 CTTTCGGGAAGCCA 156 GATGAAGCCTTTCGCAAGTTCCTGAAGGGCCTGGCTT
GGCCCT
APOC1 NM_001645 157 CCAGCCTGATAAA 158 CACTCTGAATCCTTGC 159 AGGACAGGACCTCC 160 CCAGCCTGATAAAGGTCCTGCGGGCAGGACAGGACC
CAACCA
APOE NM_000041 161 GCCTCAAGAGCTGGT 162 CCTGCACCTTCTCCAC 163 ACTGGCGCTGCATG 164 GCCTCAAGAGCTGGTTCGAGCCCCTGGTGGAAGACATGC
TCG CA TCTTCCAC AGCGCCAGTGGGCCGGGCTGGTGGAGAAGGTGC
APRT NM_000485 165 GAGGTCCTGGAGT 166 AGGTGCCAGCTTCTC 167 CCTTAAGCGAGGTC 168 GAGGTCCTGGAGTGCGTGAGCCTGGTGGAGCTGACC
AGCTCC
AQP2 NM_000486 169 GTGTGGGTGCCAG 170 CCCTTCAGCCCTCTCA 171 CTCCTTCCCTTCCC 172 GTGTGGGTGCCAGTCCTCCTCAGGAGAAGGGGAAGG
CTTCTCC
AR NM_000044 173 CGACTTCACCGCA 174 TGACACAAGTGGGAC 175 ACCATGCCGCCAGG 176 CAGCTTCACCGCACCTGATGTGTGGTACCCTGGCGG
GTACCA
ARF1 NM_001658 177 CAGTAGAGATCCC 178 ACAAGCACATGGCTA 179 CTTGTCCTTGGGTC 180 CAGTAGAGATCCCCGCAACTCGCTTGTCCTTGGGTCA
ACCCTG
ARHGAP29 NM_004815 181 CACGGTCTCGTGGTG 182 CAGTTGCTTGCCCAGG 183 ATGCCAGACCCAGA 184 CACGGTCTCGTGGTGAAGTCAATGCCAGACCCAGACAAA
AAGT AC CAAAGCATCA GCATCAGCTTGTCCTGGGCAAGCAACTG
ARHGD1 NM_001175 185 TGGTCCCTAGAAC 186 TGATGGAGGATCAGA 187 TAAAACCGGGCTTT 188 TGGTCCCTAGAACAAGAGGCTTAAAACCGGGCTTTC
CACCCA
ASAP2 NM_003887 189 CGGCCCATCAGCT 190 CTCTGGCCAAAGATA 191 CTGGGCTCCAACCA 192 CGGCCCATCAGCTTCTACCAGCTGGGCTCCAACCAG
GCTTCA
ASPN NM_017680 193 TGGACTAATCTGT 194 AAACACCCTTCAACA 195 AGTATCACCCAGGG 196 TGGACTAATCTGTGGGAGCAGTTTATTCCAGTATCAC
TGCAGC
ATM NM_000051 197 TGCTTTCTACACAT 198 GTTGTGGATCGGCTC 199 CCAGCTGTCTTCGA 200 TGCTTTCTACACATGTTCAGGGATTTTTCACCAGCTG
CACTTC
ATP5E NM_006886 201 CCGCTTTCGCTAC 202 TGGGAGTATCGGATG 203 TCCAGCCTGTCTCC 204 CCGCTTTCGCTACAGCATGGTGGCCTACTGGAGACA
AGTAGG
ATP5J NM_0010037 205 GTCGACCGACTGAAA 206 CTCTACTTCCGGCCC 207 CTACCCGCCATCGC 208 GTCGACCGACTGAAACGGCGGCCCATAATGCATTGCGAT
03 CGG TGG AATGCATTAT GGCGGGTAGGCGTGTGGGGGCGGAGCCAGGGCC
ATXN1 NM_000332 209 GATCGACTCCAGC 210 GAACTGTATCACGGC 211 CGGGCTATGGCTGT 212 GATCGACTCCAGCACCGTAGAGGATTGAAGACAG
CTTCAA
AURKA NM_003600 213 CATCTTCCAGGAG 214 TCCGACCTTCAATCAT 215 CTCTGTGGCACCCT 216 CATCTTCCAGGAGGACCACTCTCTGTGGCACCCTGGA
GGACTA
AURKB NM_004217 217 AGCTGCAGAAGAG 218 GCATCTGCCAACTCC 219 TGACGAGCAGCGAA 220 AGCTGCAGAAGAGCTGCACATTTGACGAGCAGCGAA
CAGCC
AXIN2 NM_004655 221 GGCTATGTCTTTG 222 ATCCGTCAGCGCATC 223 ACCAGCGCCAACGA 224 GGCTATGTCTTTGCACCAGCCACCAGCGCCAACGAC
CAGTG
AZGP1 NM_001185 225 GAGGCCAGCTAGG 226 CAGGAAGGGCAGCTA 227 TCTGAGATCCCACA 228 GAGGCCAGCTAGGAAGCAAGGGTTGGAGGCAATGTG
TTGCCT
BAD NM_032989 229 GGGTCAGGGGCCT 230 CTGCTCACTCGGCTC 231 TGGGCCCAGAGCAT 232 GGGTCAGGGGCCTCGAGATCGGGCTTGGGCCCAGAG
GTTCCA
BAG5 NM_001015049 233 ACTCCTGCAATGAAC 234 ACAAACAGCTCCCCAC 235 ACACCGGATTTAGC 236 ACTCCTGCAATGAACCCTGTTGACACCGGATTTAGCTCT
CCTGT GA TCTTGTCGGC TGTCGGCCTTCGTGGGGAGCTGTTTGT
BAK1 NM_001188 237 CCATTCCCACCATT 238 GGGAACATAGACCCA 239 ACACCCCAGACGTC 240 CCATTCCCACCATTCTACCTGAGGCCAGGACGTCTGG
CTGGCC
BAX NM_004324 241 CCGCCGTGGACAC 242 TTGCCGTCAGAAAAC 243 TGCCACTCGGAAAA 244 CCGCCGTGGACACAGACTCCCCCCGAGAGGTCTTTTT
AGACCT
BBC3 NM_014417 245 CCTGGAGGGTCCTGT 246 CTAATTGGGCTCCATC 247 CATCATGGGACTCC 248 CCTGGAGGGTCCTGTACAATCTCATCATGGGACTCCTGC
ACAAT TCG TGCCCTTACC CCTTACCCAGGGGCCACAGAGCCCCCGAGATGGA
BCL2 NM_000633 249 CAGATGGACCTAGTA 250 CCTATGATTTAAGGGC 251 TTCCACGCCGAAGG 252 CAGATGGACCTAGTACCCACTGAGATTTCCACGCCGAAG
CCCACTGAGA ATTTTTCC ACAGCGAT GACAGCGATGGGAAAAATGCCCTTAAATCATAG
BDKRB1 NM_000710 253 GTGGCAGAAATCT 254 GAAGGGCAAGCCCAA 255 ACCTGGCAGCCTCT 256 GTGGCAGAAATCTACCTGGCCAACCTGGCAGCCTCT
GATCTG
BGN NM_001711 257 GAGCTCCGCAAGG 258 CTTGTTGTTCACCAGG 259 CAAGGGTCTCCAGC 260 GAGCTCCGCAAGGATGACTTCAAGGGTCTCCAGCAC
ACCTCT
BIK NM_001197 261 ATTCCTATGGCTCTG 262 GGCAGGAGTGAATGGC 263 CCGGTTAACTGTGG 264 ATTCCTATGGCTCTGCAATTGTCACCGGTTAACTGTGGC
CAATTGTC TCTTC CCTGTGCCC CTGTGCCCAGGAAGAGCCATTCACTCCTGCC
BIN1 NM_004305 265 CCTGCAAAAGGGAAC 266 CGTGGTTGACTCTGAT 267 CTTCGCCTCCAGAT 268 CCTGCAAAAGGGAACAAGAGCCCTTCGCCTCCAGATGGC
AAGAG CTCG GGCTCCC TCCCCTGCCGCCACCCCCGAGATCAGAGTCAAC
BIRC5 NM_001012271 269 TTCAGGTGGATGAGG 270 CACACAGCAGTGGCAA 271 TCTGCCAGACGCTT 272 TTCAGGTGGATGAGGAGACAGAATAGAGTGATAGGAAGC
AGACA AAG CCTATCACTCTATT GTCTGGCAGATACTCCTTTTGCCACTGCTGTGTG
C
BMP6 NM_001718 273 GTGCAGACCTTGG 274 CTTAGTTGGCGCACA 275 TGAACCCCGAGTAT 276 GTGCAGACCTTGGTTCACCTTATGAACCCCGAGTATG
GTCCCC
BMPR1B NM_001203 277 ACCACTTTGGCCA 278 GCGGTGTTTGTACCC 279 ATTCACATTACCAT 280 ACCACTTTGGCCATCCCTGCATTTGGGGCCGTCTATGG
AGCGGC
BRCA1 NM_007294 281 TCAGGGGGCTAGA 282 CCATTCCAGTTGATCT 283 CTATGGGCCCTTCA 284 TCAGGGGGCTAGAAATCTGTTGCTATGGGCCCTTCAC
CCAACA
BRCA2 NM_000059 285 AGTTCGTGCTTTG 286 AAGGTAAGCTGGGTC 287 CATTCTTCACTGCT 288 AGTTCGTGCTTTGCAAGATGGTGCAGAGCTTTATGAA
TCATAA
BTG1 NM_001731 289 GAGGTCCGAGCGA 290 AGTTATTTTCGAGAC 291 CGCTCGTCTCTTCC 292 GAGGTCCGAGCGATGTGACCAGGCCGCCATCGCTCG
TCTCTC
BTG3 NM_006806 293 CCATATCGCCCAA 294 CCAGTGATTCCGGTC 295 CATGGGTACCTCCT 296 CCATATCGCCCAATTCCAGTGACATGGGTACCTCCTC
CCTGGA
BTRC NM_033637 297 GTTGGGACACAGT 298 TGAAGCAGTCAGTTG 299 CAGTCGGCCCAGGA 300 GTTGGGACACAGTTGGTCTGCAGTCGGCCCAGGACG
CGGTCT
BUB1 NM_004336 301 CCGAGGTTAATCC 302 AAGACATGGCGCTCT 303 TGCTGGGAGCCTAC 304 CCGAGGTTAATCCAGCACGTATGGGGCCAAGTGTAG
ACTTGG
C7 NM_000587 305 ATGTCTGAGTGTG 306 AGGCCTTATGCTGGT 307 ATGCTCTGCCCTCT 308 ATGTCTGAGTGTGAGGCGGGCGCTCTGAGATGCAGA
GCATCT
CACNA1D NM_000720 309 AGGACCCAGCTCCAT 310 CCTACATTCCGTGCC 311 CAGTACACTGGCGT 312 AGGACCCAGCTCCATGTGCGTTCTCAGGGAATGGACGCC
GTG ATTG CCATTCCCTG AGTGTACTGCCAATGGCACGGAATGTAGG
CADM1 NM_014333 313 CCACCACCATCCT 314 GATCCACTGCCCTGA 315 TCTTCACCTGCTCG 316 CCACCACCATCCTTACCATCATCACAGATTCCCGAGC
GGAATC
CADPS NM_003716 317 CAGCAAGGAGACT 318 GGTCCTCTTCTCCACG 319 CTCCTGGATGGCCA 320 CAGCAAGGAGACTGTGCTGAGCTCCTGGATGGCCAA
AATTTG
CASP1 NM_001223 321 AACTGGAGCTGAG 322 CATCTACGCTGTACC 323 TCACAGGCATGACA 324 AACTGGAGCTGAGGTTGACATCACAGGCATGACAAT
ATGCTG
CASP3 NM_032991 325 TGAGCCTGAGCAG 326 CCTTCCTGCGTGGTCC 327 TCAGCCTGTTCCAT 328 TGAGCCTGAGCAGAGACATGACTCAGCCTGTTCCAT
GAAGGC
CASP7 NM_033338 329 GCAGCGCCGAGAC 330 AGTCTCTCTCCGTCGC 331 CTTTCGCTAAAGGG 332 GCAGCGCCGAGACTTTAGTTTCGCTTTCGCTAAAGG
GCCCCA
CAV1 NM_001753 333 GTGGCTCAACATT 334 CAATGGCCTCCATTTT 335 ATTTCAGCTGATCA 336 GTGGCTCAACATTGTGTTCCCATTTCAGCTGATCAGT
GTGGGC
CAV2 NM_198212 337 CTTCCCTGGGACG 338 CTCCTGGTCACCCTTC 339 CCCGTACTGTCATG 340 CTTCCCTGGGACGACTTGCCAGCTCTGAGGCATGAC
CCTCAG
CCL2 NM_002982 341 CGCTCAGCCAGATGC 342 GCACTGAGATCTTCCT 343 TGCCCCAGTCACCT 344 CGCTCAGCCAGATGCAATCAATGCCCCAGTCACCTGCTG
AATC ATTGGTGAA GCTGTTA TTATAACTTCACCAATAGGAAGATCTCAGTGC
CCL5 NM_002985 345 AGGTTCTGAGCTC 346 ATGCTGACTTCCTTCC 347 ACAGAGCCCTGGCA 348 AGGTTCTGAGCTCTGGCTTTGCCTTGGCTTTGCCAGG
AAGCC
CCNB1 NM_031996 349 TTCAGGTTGTTGCAG 350 CATCTTCTTGGGCACA 351 TGTCTCCATTATGA 352 TTCAGGTTGTTGCAGGAGACCATGTACATGACTGTCTCC
GAGAC CAAT TCGGTTCATGCA ATTATTGATCGGTTCATGCAGAATAATTGTGTGCC
CCND1 NM_001758 353 GCATGTTCGTGGC 354 CGGTGTAGATGCACA 355 AAGGAGACCATCCC 356 GCATGTTCGTGGCCTCTAAGATGAAGGAGACCATCC
CCTGAC
CCNE2 NM_057749 357 ATGCTGTGGCTCCTT 358 ACCCAAATTGTGATAT 359 TACCAAGCAACCTA 360 ATGCTGTGGCTCCTTCCTAACTGGGGCTTTCTTGACATGT
CCTAACT ACAAAAAGGTT CATGTCAAGAAAGC AGGTTGCTTGGTAATAACCTTTTTGTATATCACA
CC
CCNH NM_001239 361 GAGATCTTCGGTG 362 CTGCAGACGAGAACC 363 CATCAGCGTCCTGG 364 GAGATCTTCGGTGGGGGTACGGGTGTTTTACGCCAG
CGTAAA
CCR1 NM_001295 365 TCCAAGACCCAAT 366 TCGTAGGCTTTCGTG 367 ACTCACCACACCTG 368 TCCAAGACCCAATGGGAATTCACTCACCACACCTGC
CAGCCT
CD164 NM_006016 369 CAACCTGTGCGAA 370 ACACCCAAGACCAGGC 371 CCTCCAATGAAACT 372 CAACCTGTGCGAAAGTCTACCTTTGATGCAGCCAGTT
GGCTGC
CD1A NM_001763 373 GGAGTGGAAGGAACT 374 TCATGGGCGTATCTAG 375 CGCACCATTCGGTC 376 GGAGTGGAAGGAACTGGAAACATTATTCCGTATACGCAC
GGAAA AAT ATTTGAGG CATTCGGTCATTTGAGGGAATTCGTAGATACGCC
CD276 NM_001024736 377 CCAAAGGATGCGATA 378 GGATGACTTGGGAATC 379 CCACTGTGCAGCCT 380 CCAAAGGATGCGATACACAGACCACTGTGCAGCCTTATT
CACAG ATGTC TATTTCTCCAATG TCTCCAATGGACATGATTCCCAAGTCATCC
CD44 NM_000610 381 GGCACCACTGCTT 382 GATGCTCATGGTGAA 383 ACTGGAACCCAGAA 384 GGCACCACTGCTTATGAAGGAAACTGGAACCCAGAA
GCACA
CD68 NM_001251 385 TGGTTCCCAGCCC 386 CTCCTCCACCCTGGGT 387 CTCCAAGCCCAGAT 388 TGGTTCCCAGCCCTGTGTCCACCTCCAAGCCCAGATT
TCAGAT
CD82 NM_002231 389 GTGCAGGCTCAGGTG 390 GACCTCAGGGCGATTC 391 TCAGCTTCTACAAC 392 GTGCAGGCTCAGGTGAAGTGCTGCGGCTGGGTCAGCTTC
AAGTG ATGA TGGACAGACAACGC TACAACTGGACAGACAACGCTGAGCTCATGAAT
TG
CDC20 NM_001255 393 TGGATTGGAGTTC 394 GCTTGCACTCCACAG 395 ACTGGCCGTGGCAC 396 TGGATTGGAGTTCTGGGAATGTACTGGCCGTGGCAC
TGGACA
CDC25B NM_021873 397 GCTGCAGGACCAG 398 TAGGGCAGCTGGCTT 399 CTGCTACCTCCCTT 400 GCTGCAGGACCAGTGAGGGGCCTGCGCCAGTCCTGC
GCCTTT
CDC6 NM_001254 401 GCAACACTCCCCA 402 TGAGGGGACCATTC 403 TTGTTCTCCACCAA 404 GCAACACTCCCCATTTACCTCCTTGTTCTCCACCAAA
AGCAAG
CDH1 NM_004360 405 TGAGTGTCCCCCGGT 406 CAGCCGCTTTCAGAT 407 TGCCAATCCCGATG 408 TGAGTGTCCCCCGGTATCTTCCCCGCCCTGCCAATCCCG
ATCTTC TTTCAT AAATTGGAAATTT ATGAAATTGGAAATTTTATTGATGAAAATCTGAAA
CDH10 NM_006727 409 TGTGGTGCAAGTC 410 TGTAAATGACTCTGG 411 ATGCCGATGACCCT 412 TGTGGTGCAAGTCACAGCTACAGATGCCGATGACCC
TCATAT
CDH11 NM_001797 413 GTCGGCAGAAGCA 414 CTACTCATGGGCGGG 415 CCTTCTGCCCATAG 416 GTCGGCAGAAGCAGGACTTGTACCTTCTGCCCATAG
TGATCA
CDH19 NM_021153 417 AGTACCATAATGC 418 AGACTGCCTGTATAG 419 ACTCGGAAAACCAC 420 AGTACCATAATGCGGGAACGCAAGACTCGGAAAACC
AAGCG
CDH5 NM_001795 421 ACAGGAGACGTGT 422 CAGCAGTGAGGTGGT 423 TATTCTCCCGGTCC 424 ACAGGAGACGTGTTCGCCATTGAGAGGCTGGACCGG
AGCCTC
CDH7 NM_033646 425 GTTTGACATGGCT 426 AGTCACATCCCTCCG 427 ACCTCAACGTCATC 428 GTTTGACATGGCTGCACTGAGAAACCTCAACGTCATC
CGAGAC
CDK14 NM_012395 429 GCAAGGTAAATGG 430 GATAGCTGTGAAAGG 431 CTTCCTGCAGCCTG 432 GCAAGGTAAATGGGAAGTTGGTAGCTCTGAAGGTGA
ATCACC
CDK2 NM_001798 433 AATGCTGCACTACGA 434 TTGGTCACATCCTGG 435 CCTTGGCCGAAATC 436 AATGCTGCACTACGACCCTAACAAGCGGATTTCGGCCAA
CCCTA AAGAA CGCTTGT GGCAGCCCTGGCTCACCTTTCTTCCAGGATGTG
CDK3 NM_001258 437 CCAGGAAGGGACT 438 GTTGCATGAGCAGGT 439 CTCTGGCTCCAGAT 440 CCAGGAAGGGACTGGAAGAGATTGTGCCCAATCTGG
TGGGCA
CDK7 NM_001799 441 GTCTCGGGCAAAG 442 CTCTGGCCTTGTAAA 443 CCTCCCCAAGGAAG 444 GTCTCGGGCAAAGCGTTATGAGAAGCTGGACTTCCT
TCCAGC
CDKN1A NM_000389 445 TGGAGACTCTCAG 446 GGCGTTTGGAGTGGT 447 CGGCGGCAGACCAG 448 TGGAGACTCTCAGGGTCGAAAACGGCGGCAGACCAG
CATGA
CDKN1C NM_000076 449 CGGCGATCAAGAA 450 CAGGCGCTGATCTCT 451 CGGGCCTCTGATCT 452 CGGCGATCAAGAAGCTGTCCGGGCCTCTGATCTCCG
CCGATT
CDKN2B NM_004936 453 GACGCTGCAGAGC 454 GCGGGAATCTCTCCT 455 CACAGGATGCTGGC 456 GACGCTGCAGAGCACCTTTGCACAGGATGCTGGCCT
CTTTGC
CDKN2C NM_001262 457 GAGCACTGGGCAA 458 CAAAGGCGAACGGGA 459 CCTGTAACTTGAGG 460 GAGCACTGGGCAATCGTTACGACCTGTAACTTGAGG
GCCACC
CDKN3 NM_005192 461 TGGATCTCTACC 462 ATGTCAGGAGTCCCT 463 ATCACCCATCATCA 464 TGGATCTCTACCAGCAATGTGGAATTATCACCCATCA
TCCAAT
CDS2 NM_003818 465 GGGCTTCTTTGCT 466 ACAGGGCAGACAAAG 467 CCCGGACATCACAT 468 GGGCTTCTTTGCTACTGTGGTGTTTGGCCTTCTGCTG
AGGACA
CENPF NM_016343 469 CTCCCGTCAACAG 470 GGGTGAGTCTGGCCT 471 ACACTGGACCAGGA 472 CTCCCGTCAACAGCGTTCTTTCCAAACACTGGACCAG
GTGCAT
CHAF1A NM_005483 473 GAACTCAGTGTAT 474 GCTCTGTAGCACCTG 475 TGCACGTACCAGCA 476 GAACTCAGTGTATGAGAAGCGGCCTGACTTCAGGAT
CATCCT
CHN1 NM_001822 477 TTACGACGCTCGT 478 TCTCCCTGATGCACAT 479 CCACCATTGGCCGC 480 TTACGACGCTCGTGAAAGCACATACCACTAAGCGGC
TTAGTG
CHRAC1 NM_017444 481 TCTCGCTGCCTCTA 482 CCTGGTTGATGCTGG 483 ATCCGGGTCATCAT 484 TCTCGCTGCCTCTATCCCGCATCCGGGTCATCATGAA
GAAGAG
CKS2 NM_001827 485 GGCTGGACGTGGT 486 CGCTGCAGAAAATGA 487 CTGCGCCCGCTCTT 488 GGCTGGACGTGGTTTTGTCTGCTGCGCCCGCTCTTCG
CGCG
CLDN3 NM_001306 489 ACCAACTGCGTGC 490 GGCGAGAAGGAACAG 491 CAAGGCCAAGATCA 492 ACCAACTGCGTGCAGGACGACACGGCCAAGGCCAAG
CCATCG
CLTC NM_004859 493 ACCGTATGGACAG 494 TGACTACAGGATCAG 495 TCTCACATGCTGTA 496 ACCGTATGGACAGCCACAGCCTGGCTTTGGGTACAG
CCCAAA
COL11A NM_001854 497 GCCCAAGAGGGGA 498 GGACCTGGGTCTCCA 499 CTGCTCGACCTTTG 500 GCCCAAGAGGGGAAGATGGCCCTGAAGGACCCAAAG
GGTCCT
COL1A1 NM_000088 501 GTGGCCATCCAGC 502 CAGTGGTAGGTGATG 503 TCCTGCGCCTGATG 504 GTGGCCATCCAGCTGACCTTCCTGCGCCTGATGTCCA
TCCACC
COL1A2 NM_000089 505 CAGCCAAGAACTGGT 506 AAACTGGCTGCCAGCA 507 TCTCCTAGCCAGAC 508 CAGCCAAGAACTGGTATAGGAGCTCCAAGGACAAGAAAC
ATAGGAGCT TTG GTGTTTCTTGTCCT ACGTCTGGCTAGGAGAAACTATCAATGCTGGCA
TG
COL3A1 NM_000090 509 GGAGGTTCTGGAC 510 ACCAGGACTGCCACG 511 CTCCTGGTCCCCAA 512 GGAGGTTCTGGACCTGCTGGTCCTCCTGGTCCCCAAG
GGTGTC
COL4A1 NM_001845 513 ACAAAGGCCTCCC 514 GAGTCCCAGGAAGAC 515 CTCCTTTGACACCA 516 ACAAAGGCCTCCCAGGATTGGATGGCATCCCTGGTG
GGGATG
COL5A1 NM_000093 517 CTCCCTGGGAAAG 518 CTGGACCAGGAAGCC 519 CCAGGGAAACCACG 520 CTCCCTGGGAAAGATGGCCCTCCAGGATTACGTGGT
TAATCC
COL5A2 NM_000393 521 GGTCGAGGAACCC 522 GCCTGGAGGTCCAAC 523 CCAGGAAATCCTGT 524 GGTCGAGGAACCCAAGGTCCGCCTGGTGCTACAGGA
AGCACC
COL6A1 NM_001848 525 GGAGACCCTGGTG 526 TCTCCAGGGACACCA 527 CTTCTCTTCCCTGA 528 GGAGACCCTGGTGAAGCTGGCCCGCAGGGTGATCAG
TCACCC
COL6A3 NM_004369 529 GAGAGCAAGCGAG 530 AACAGGGAACTGGCC 531 CCTCTTTGACGGCT 532 GAGAGCAAGCGAGACATTCTGTTCCTCTTTGACGGCT
CAGCCA
COL8A1 NM_001850 533 TGGTGTTCCAGGG 534 CCCTGTAAACCCTGA 535 CCTAAGGGAGAGCC 536 TGGTGTTCCAGGGCTTCTCGGACCTAAGGGAGAGCC
AGGAA
COL9A2 NM_001852 537 GGGAACCATCCAG 538 ATTCCGGGTGGACAG 539 ACACAGGAAATCCG 540 GGGAACCATCCAGGGTCTGGAAGGCAGTGCGGATTT
CACTGC
CRISP3 NM_006061 541 TCCCTTATGAACA 542 AACCATTGGTGCATA 543 TGCCAGTTGCCCAG 544 TCCCTTATGAACAAGGAGCACCTTGTGCCAGTTGCCC
ATAACT
CSF1 NM_000757 545 TGCAGCGGCTGATTG 546 CAACTGTTCCTGGTC 547 TCAGATGGAGACCT 548 TGCAGCGGCTGATTGACAGTCGATGGAGACCTCGTGCCA
ACA TACAAACTCA CGTGCCAAATTACA AATTACATTTGAGTTTGTAGACCAGGAACAGTT
CSK NM_004383 549 CCTGAACATGAAG 550 CATCACGTCTCCGAA 551 TCCCGATGGTCTGC 552 CCTGAACATGAAGGAGCTGAAGCTGCTGCAGACCAT
AGCAGC
CSRP1 NM_004078 553 ACCCAAGACCCTG 554 GCAGGGGTGGAGTGA 555 CCACCCTTCTCCAG 556 ACCCAAGACCCTGCCTCTTCCACTCCACCCTTCTCCA
GGACCC
CTGF NM_001901 557 GAGTTCAAGTGCCCT 558 AGTTGTAATGGCAGGC 559 AACATCATGTTCTT 560 GAGTTCAAGTGCCCTGACGGCGAGGTCATGAAGAAGAAC
GACG ACAG CTTCATGACCTCGC ATGATGTTCATCAAGACCTGTGCCTGCCATTACA
CTHRC1 NM_138455 561 TGGCTCACTTCGG 562 TCAGCTCCATTGAAT 563 CAACGCTGACAGCA 564 TGGCTCACTTCGGCTAAAATGCAGAAATGCATGCTGT
TGCATT
CTNNA1 NM_001903 565 CGTTCCGATCCTCTA 566 AGGTCCCTGTTGGCCT 567 ATGCCTACAGCACC 568 CGTTCCGATCCTCTATACTGCATCCCAGGCATGCCTACA
TACTGCAT TATAGG CTGATGTCGCA GCACCCTGATGTCGCAGCCTATAAGGCCAACAGG
CTNNB1 NM_001904 569 GGCTCTTGTGCGTAC 570 TCAGATGACGAAGAGC 571 AGGCTCAGTGATGT 572 GGCTCTTGTGCGTACTGTCCTTCGGGCTGGTGACAGGGA
TGTCCTT ACAGATG CTTCCCTGTCACCA AGACATCACTGAGCCTGCCATCTGTGCTCTTCGTC
G
CTNND1 NM_001331 573 CGGAAACTTCGGG 574 CTGAATCCTTCTGCCC 575 TTGATGCCCTCATT 576 CGGAAACTTCGGGAATGTGATGGTTTAGTTGATGCC
TTCATT
CTNND2 NM_001332 577 GCCCGTCCCTACA 578 CTCACACCCAGGAGT 579 CTATGAAACGAGCC 580 GCCCGTCCCTACAGTGAACTGAACTATGAAACGAGC
ACTACC
CTSB NM_001908 581 GGCCGAGATCTAC 582 GCAGGAAGTCCGAAT 583 CCCCGTGGAGGGAG 584 GGCCGAGATCTACAAAAACGGCCCCGTGGAGGGAGC
CTTTCT
CTSD BN_001909 585 GTACATGATCCCCTG 586 GGGACAGCTTGTAGCC 587 ACCCTGCCCGCGAT 588 GTACATGATCCCCTGTGAGAAGGTGTCCACCCTGCCCGC
TGAGAAGGT TTTGC CACACTGA GATCACACTGAAGCTGGGAGGCAAAGGCTACAAG
CTSK NM_000396 589 AGGCTTCTCTTGG 590 CCACCTCTTCACTGGT 591 CCCCAGGTGGTTCA 592 AGGCTTCTCTTGGTGTCCATACATATGAACTGGCTAT
TAGCCA
CTSL2 NM_001333 593 TGTCTCACTGAGC 594 ACCATTGCAGCCCTG 595 CTTGAGGACGCGAA 596 TGTCTCACTGAGCGAGCAGAATCTGGTGGACTGTTC
CAGTCC
CTSS NM_004079 597 TGACAACGGCTTT 598 TCCATGGCTTTGTAG 599 TGATAACAAGGGCA 600 TGACAACGGCTTTCCAGTACATCATTGATAACAAGG
TCGACT
CUL1 NM_003592 601 ATGCCCTGGTAAT 602 GCGACCACAAGCCTT 603 CAGCCACAAAGCCA 604 ATGCCCTGGTAATGTCTGCATTCAACAATGACGCTGG
GCGTCA
CXCL12 NM_000609 605 GAGCTACAGATGC 606 TTTGAGATGCTTGAC 607 TTCTTCGAAAGCCA 608 GAGCTACAGATGCCCATGCCGATTCTTCGAAAGCCA
TGTTGC
CXCR4 NM_003467 609 TGACCGCTTCTAC 610 AGGATAAGGCCAACC 611 CTGAAACTGGAACA 612 TGACCGCTTCTACCCCAATGACTTGTGGGTGGTTGTG
CAACCA
CXCR7 NM_020311 613 CGCCTCAGAACGATG 614 GTTGCATGGCCAGCTG 615 CTCAGAGCCAGGGA 616 CGCCTCAGAACGATGGATCTGCATCTTCGACTACTCAGA
GAT AT ACTTCTCGGA GCCAGGGAACTTCTCGGACATCAGCTGGCCAT
CYP3A5 NM_000777 617 TCATTGCCCAGTA 618 GACAGGCTTGCCTTT 619 TCCCGCCTCAAGTT 620 TCATTGCCCAGTATGGAGATGTATTGGTGAGAAACTT
TCTCAC
CYR61 NM_001554 621 TGCTCATTCTTGAG 622 GTGGCTGCATTAGTG 623 CAGCACCCTTGGCA 624 TGCTCATTCTTGAGGAGCATTAAGGTATTTCGAAACT
GTTTCG
DAG1 NM_004393 625 GTGACTGGGCTCA 626 ATCCCACTTGTGCTCC 627 CAAGTCAGAGTTTC 628 GTGACTGGGCTCATGCCTCCAAGTCAGAGTTTCCCTG
CCTGGT
DAP NM_004394 629 CCAGCCTTTCTGG 630 GACCAGGTCTGCCTC 631 CTCACCAGCTGGCA 632 CCAGCCTTTCTGGTGCTGTTCTCCAGTTCACGTCTGC
GACGTG
DAPK1 NM_004938 633 CGCTGACATCATG 634 TCTCTTTCAGCAACGA 635 TCATATCCAAACTC 636 CGCTGACATCATGAATGTTCCTCGACCGGCTGGAGG
GCCTCC
DARC NM_002036 637 GCCCTCATTAGTC 638 CAGACAGAAGGGCTG 639 TCAGCGCCTGTGCT 640 GCCCTCATTAGTCCTTGGCTCTTATCTTGGAAGCACA
TCCAAG
DDIT4 NM_019058 641 CCTGGCGTCTGTC 642 CGAAGAGGAGGTGGA 643 CTAGCCTTTGGGAC 644 CCTGGCGTCTGTCCTCACCATGCCTAGCCTTTGGGAC
CGCTTC
DDR2 NM_001014796 645 CTATTACCGGATCCA 646 CCCAGCAAGATACTCT 647 AGTGCTCCCTATCC 648 CTATTACCGGATCCAGGGCCGGGCAGTGCTCCCTATCCG
GGGC CCCA GCTGGATGTC CTGGATGTCTTGGGAGAGTATCTTGCTGGG
DES NM_001927 649 ACTTCTCACTGGC 650 GCTCCACCTTCTCGTT 651 TGAACCAGGAGTTT 652 ACTTCTCACTGGCCGACGCGGTGAACCAGGAGTTTCT
CTGACC
DHRS9 NM_005771 653 GGAGAAAGGTCTC 654 CAGTCAGTGGGAGCC 655 ATCAATAATGCTGG 656 GGAGAAAGGTCTCTGGGGTCTGATCAATAATGCTGG
TGTTCC
DHX9 NM_001357 657 GTTCGAACCATCT 658 TCCAGTTGGATTGTG 659 CCAAGGAACCACAC 660 GTTCGAACCATCTCAGCGACAAAACCAAGTGGGTGT
CCACTT
DIAPH1 NM_005219 661 CAAGCAGTCAAGG 662 AGTTTTGCTCGCCTCA 663 TTCTTCTGTCTCCC 664 CAAGCAGTCAAGGAGAACCAGAAGCGGCGGGAGAC
GCCGCT
DICER1 NM_177438 665 TCCAATTCCAGCA 666 GGCAGTGAAGGCGAT 667 AGAAAAGCTGTTTG 668 TCCAATTCCAGCATCACTGTGGAGAAAAGCTGTTTGT
TCTCCC
DIO2 NM_013989 669 CTCCTTTCACGAG 670 AGGAAGTCAGCCACT 671 ACTCTTCCACCAGT 672 CTCCTTTCACGAGCCAGCTGCCAGCCTTCCGCAAACT
TTGCGG
DLC1 NM_006094 673 GATTCAGACGAGG 674 CACCTCTTGCTGTCCC 675 AAAGTCCATTTGCC 676 GATTCAGACGAGGATGAGCCTTGTGCCATCAGTGGC
ACTGAT
DLGAP1 NM_004746 677 CTGCTGAGCCCAG 678 AGCCTGGAAGGAGTT 679 CGCAGACCACCCAT 680 CTGCTGAGCCCAGTGGAGCACCACCCCGCAGACCAC
ACTACA
DLL4 NM_019074 681 CACGGAGGTATAA 682 AGAAGGAAGGTCCAG 683 CTACCTGGACATCC 684 CACGGAGGTATAAGGCAGGAGCCTACCTGGACATCC
CTGCTC
DNM3 NM_015569 685 CTTTCCCACCCGG 686 AAGGACCTTCTGCAG 687 CATATCGCTGACCG 688 CTTTCCCACCCGGCTTACAGACATATCGCTGACCGAA
AATGGG
DPP4 NM_001935 689 GTCCTGGGATCGG 690 GTACTCCCACCGGGA 691 CGGCTATTCCACAC 692 GTCCTGGGATCGGGAAGTGGCGTGTTCAAGTGTGGA
TTGAAC
DPT NM_001937 693 CACCTAGAAGCCT 694 CAGTAGCTCCCCAGG 695 TTCCTAGGAAGGCT 696 CACCTAGAAGCCTGCCCACGATTCCTAGGAAGGCTG
GGCAGA
DUSP1 NM_004417 697 AGACATCAGCTCC 698 GACAAACACCCTTCC 699 CGAGGCCATTGACT 700 AGACATCAGCTCCTGGTTCAACGAGGCCATTGACTTC
TCATAG
DUSP6 NM_001946 701 CATGCAGGGACTG 702 TGCTCCTACCCTATCA 703 TCTACCCTATGCGC 704 CATGCAGGGACTGGGATTCGAGGACTTCCAGGCGCA
CTGGAA
DVL1 NM_004421 705 TCTGTCCCACCTG 706 TCAGACTGTTGCCGG 707 CTTGGAGCAGCCTG 708 TCTGTCCCACCTGCTGCTGCCCCTTGGAGCAGCCTGC
CACCTT
DYNLL1 NM_001037494 709 GCCGCCTACCTCACA 710 GCCTGACTCCAGCTCT 711 ACCCACGTCAGTGA 712 GCCGCCTACCTCACAGACTTGTGAGCACTCACTGACGTG
GAC CCT GTGCTCACAA GGTAGCGCCCAGGGCCTGCGGGGCGCAGGAGAG
EBNA1BP2 NM_006824 713 TGCGGCGAGATGGAC 714 GTGACAAGGGATTCAT 715 CCCGCTCTCGGATT 716 TGCGGCGAGATGGACACTCCCCCGCTCTCGGATTCGGAG
ACT CGGATT CGGAGTCG TCGGAATCCGATGAATCCCTTGTCAC
ECE1 NM_001397 717 ACCTTGGGATCTG 718 GGACCAGGACCTCCA 719 TCCACTCTCGATAC 720 ACCTTGGGATCTGCCTCCAAGCTGGTGCAGGGTATC
CCTGCA
EDN1 NM_001955 721 TGCCACCTGGACA 722 TGGACCTAGGGCTTC 723 CACTCCCGAGCACG 724 TGCCACCTGGACATCATTTGGGTCAACACTCCCGAGC
TTGTTC
EDNRA NM_001957 725 TTTCCTCAAATTTG 726 TTACACATCCAACCA 727 CCTTTGCCTCAGGG 728 TTTCCTCAAATTTGCCTCAAGATGGAAACCCTTTGCC
CATCCT
EFNB2 NM_004093 729 TGACATTATCATCCC 730 GTAGTCCCCGCTGACC 731 CGGACAGCGTCTTC 732 TGACATTATCATCCCGCTAAGGACTGCGGACAGCGTCTT
GCTAAGGA TTCTC TGCCCTCACT CTGCCCTCACTACGAGAAGGTCAGCGGGGACTA
EGF NM_001963 733 CTTTGCCTTGCTCTG 734 AAATACCTGACACCCT 735 AGAGTTTAACAGCC 736 CTTTGCCTTGCTCTGTCACAGTGAAGTCAGCCAGAGCAG
TCACAGT TATGACAAATT CTGCTCTGGCTGAC GGCTGTTAAACTCTGTGAAATTTGTCATAAGGGTG
TT
EGR1 NM_001964 737 GTCCCCGCTGCAGAT 738 CTCCAGCTTAGGGTAG 739 CGGATCCTTTCCTC 740 GTCCCCGCTGCAGATCTCTGACCCGTTCGGATCCTTTCC
CTCT TTGTCCAT ACTCGCCCA TACTCGCCCACCATGGACAACTACCCTAAGCTGG
EGR3 NM_004430 741 CCATGTGGATGAATG 742 TGCCTGAGAAGAGGTG 743 ACCCAGTCTCACCT 744 CCATGTGGATGAATGAGGTGTCTCCTTTCCATACCCAGT
AGGTG AGGT TCTCCCCACC CTCACCTTCTCCCCACCCTACCTCACCTCTTCTCA
EIF2C2 NM_012154 745 GCACTGTGGGCAG 746 ATGTTTGGTGACTGG 747 CGGGTCACATTGCA 748 GCACTGTGGGCAGATGAAGAGGAAGTACCGCGTCTG
GACACG
EIF2S3 NM_001415 749 CTGCCTCCCTGATT 750 GGTGGCAAGTGCCTG 751 TCTCGTGCTTCAGC 752 CTGCCTCCCTGATTCAAGTGATTCTCGTGCTTCAGCC
CTCCCA
EIF3H NM_003756 753 CTCATTGCAGGCCAG 754 GCCATGAAGAGCTTGC 755 CAGAACATCAAGGA 756 CTCATTGCAGGCCAGATAAACACTTACTGCCAGAACATC
ATAAA CTA GTTCACTGCCCA AAGGAGTTCACTGCCCAAAACTTAGGCAAGCTC
EIF4E NM_001968 757 GATCTAAGATGGCGA 758 TTAGATTCCGTTTTCT 759 ACCACCCCTACTCC 760 GATCTAAGATGGCGACTGTCGAACCGGAAACCACCCCTA
CTGTCGAA CCTCTTCTG TAATCCCCCGACT CTCCTAATCCCCCGACTACAGAAGAGGAGAAAA
EIF5 NM_001969 761 GAATTGGTCTCCA 762 TCCAGGTATATGGCT 763 CCACTTGCACCCGA 764 GAATTGGTCTCCAGCTGCCTTTGATCAAGATTCGGGT
ATCTTG
ELK4 NM_001973 765 GATGTGGAGAATG 766 AGTCATTGCGGCTAG 767 ATAAACCACCTCAG 768 GATGTGGAGAATGGAGGGAAAGATAAACCACCTCAG
CCTGGT
ENPP2 NM_006209 769 CTCCTGCGCACTA 770 TCCCTGGATAATTGG 771 TAACTTCCTCTGGC 772 CTCCTGCGCACTAATACCTTCAGGCCAACCATGCCAG
ATGGTT
ENY2 NM_020189 773 CCTCAAAGAGTTG 774 CCTCTTTACAGTGTGC 775 CTGATCCTTCCAGC 776 CCTCAAAGAGTTGCTGAGAGCTAAATTAATTGAATGT
CACATT
EPHA2 NM_004431 777 CGCCTGTTCACCA 778 GTGGCGTGCCTCGAA 779 TGCGCCCGATGAGA 780 CGCCTGTTCACCAAGATTGACACCATTGCGCCCGATG
TCACCG
EPHA3 NM_005233 781 CAGTAGCCTCAAG 782 TTCGTCCCATATCCAG 783 TATTCCAAATCCGA 784 CAGTAGCCTCAAGCCTGACACTATATACGTATTCCAA
GCCCGA
EPHB2 NM_004442 785 CAACCAGGCAGCT 786 GTAATGCTGTCCACG 787 CACCTGATGCATGA 788 CAACCAGGCAGCTCCATCGGCAGTGTCCATCATGCA
TGGACA
EPHB4 NM_004444 789 TGAACGGGGTATCCT 790 AGGTACCTCTCGGTCA 791 CGTCCCATTTGAGC 792 TGAACGGGGTATCCTCCTTAGCCAGGGGCCCGTCCCATT
CCTTA GTGG CTGTCAATGT TGAGCCTGTCAATGTCACCACTGACCGAGAGGT
ERBB2 NM_004448 793 CGGTGTGAGAAGT 794 CCTCTCGCAAGTGCT 795 CCAGACCATAGCAC 796 CGGTGTGAGAAGTGCAGCAAGCCCTGTGCCCGAGTG
ACTCGG
ERBB3 NM_001982 797 CGGTTATGTCATGCC 798 GAACTGAGACCCACTG 799 CCTCAAAGGTACTC 800 CGGTTATGTCATGCCAGATACACACCTCAAAGGTACTCC
AGATACAC AAGAAAGG CCTCCTCCCGG CTCCTCCCGGGAAGGCACCCTTTCTTCAGTGGGTC
ERBB4 NM_005235 801 TGGCTCTTAATCAGT 802 CAAGGCATATCGATCC 803 TGTCCCACGAATAA 804 TGGCTCTTAATCAGTTTCGTTACCTGCCTCTGGAGAATT
TTCGTTACCT TCATAAAGT TGCGTAAATTCTCC TACGCATTATTCGTGGGACAAAACTTTATGAGGAT
AG
ERCC1 NM_001983 805 GTCCAGGTGGATG 806 CGGCCAGGATACACA 807 CAGCAGGCCCTCAA 808 GTCCAGGTGGATGTGAAAGATCCCCAGCAGGCCCTC
GGAGCT
EREG NM_001432 809 TGCTAGGGTAAAC 810 TGGAGACAAGTCCTG 811 TAAGCCATGGCTGA 812 TGCTAGGGTAAACGAAGGCATAATAAGCCATGGCTG
CCTCTG
ERG NM_004449 813 CCAACACTAGGCT 814 CCTCCGCCAGGTCTTT 815 AGCCATATGCCTTC 816 CCAACACTAGGCTCCCCACCAGCCATATGCCTTCTCA
TCATCT
ESR1 NM_000125 817 CGTGGTGCCCCTC 818 GGCTAGTGGGCGCAT 819 CTGGAGATGCTGGA 820 CGTGGTGCCCCTCTATGACCTGCTGCTGGAGATGCTG
CGCCC
ESR2 NM_001437 821 TGGTCCATCGCCAGT 822 TGTTCTAGCGATCTTG 823 ATCTGTATGCGGAA 824 TGGTCCATCGCCAGTTATCACATCTGTATGCGGAACCTC
TATCA CTTCACA CCTCAAAAGAGTCC AAAAGAGTCCCTGGTGTGAAGCAAGATCGCTAGA
CT
ETV1 NM_004956 825 TCAAACAAGAGCC 826 AACTGCCAGAGCTGA 827 ATCGGGAAGGACCC 828 TCAAACAAGAGCCAGGAATGTATCGGGAAGGACCCA
ACATAC
ETV4 NM_001986 829 TCCAGTGCCTATG 830 ACTGTCCAAGGGCAC 831 CAGACAAATCGCCA 832 TCCAGTGCCTATGACCCCCCCAGACAAATCGCCATCA
TCAAGT
EZH2 NM_004456 833 TGGAAACAGCGAAGG 834 CACCGAACACTCCCTA 835 TCCTGACTTCTGTG 836 TGGAAACAGCGAAGGATACAGCCTGTGCACATCCTGACT
ATACA GTCC AGCTCATTGCG TCTGTGAGCTCATTGCGCGGGACTAGGGAGTGTT
F2R NM_001992 837 AAGGAGCAAACCA 838 GCAGGGTTTCATTGA 839 CCCGGGCTCAACAT 840 AAGGAGCAAACCATCCAGGTGCCCGGGCTCAACATC
CACTAC
FAAH NM_001441 841 GACAGCGTAGTGGTG 842 AGCTGAACATGGACTG 843 TGCCCTTCGTGCAC 844 GACAGCGTGGTGGTGCATGTGCTGAAGCTGCAGGGTGCC
CATGT TGGA ACCAATG GTGCCCTTCGTGCACACCAATGTTCCACAGTCCA
FABP5 NM_001444 845 GCTGATGGCGAGAAA 846 CTTTCCTTCCCATCCC 847 CCTGATGCTGAACC 848 GCTGATGGCAGAAAAACTCAGACTGTCTGCAACTTTACA
AACTCA ACT AATGCACCAT GATGGTGCATTGGTTCAGCATCAGGAGTGGGAT
FADD NM_003824 849 GTTTTCGCGAGAT 850 CTCCGGTGCCTGATTC 851 AACGCGCTCTTGTC 852 GTTTTCGCGAGATAACGGTCGAAAACGCGCTCTTGTC
GATTTC
FAM107 NM_007177 853 AAGTCAGGGAAAA 854 GCTGGCCCTACAGCT 855 AATTGCCACACTGA 856 AAGTCAGGGAAAACCTGCGGAGAATTGCCACACTGA
CCAGCG
FAM13C NM_198215 857 ATCTTCAAAGCGG 858 GCTGGATACCACATG 859 TCCTGACTTTCTCC 860 ATCTTCAAAGCGGAGAGCGGGAGGAGCCACGGAGAA
GTGGCT
FAM171B NM_177454 861 CCAGGAAGGAAAAGC 862 GTGGTCTGCCCCTTCT 863 TGAAGATTTTGAAG 864 CCAGGAAGGAAAAGCACTGTTGAAGATTTTGAAGCTAAT
ACTGT TTTA CTAATACATCCCCC ACATCCCCCACTAAAAGAAGGGGCAGACCAC
AC
FAM49B NM_016623 865 AGATGCAGAAGGC 866 GCTGGATTGCCTCTC 867 TGGCCAGCTCCTCT 868 AGATGCAGAAGGCATCTTGGAGGACTTGCAGTCATA
GTATGA
FAM73A NM_198549 869 TGAGAAGGTGCGCTA 870 GGCCATTAAAAGCTCA 871 AAGACCTCATGCAG 872 TGAGAAGGTGCGCTATTCAAGTACAGAGACTTTAGCTGA
TTCAA GTGC TTACTCATTCGCC AGACCTCATGCAGTTACTCATTCGCCGCACTGAG
FAP NM_004460 873 GTTGGCTCACGTG 874 GACAGGACCGAAACA 875 AGCCACTGCAAACA 876 GTTGGCTCACGTGGGTTACTGATGAACGAGTATGTTT
TACTCG
FAS NM_000043 877 GGATTGCTCAACAAC 878 GGCATTAACACTTTTG 879 TCTGGACCCTCCTA 880 GGATTGCTCAACAACCATGCTGGGCATCTGGACCCTCCT
CATGCT GACGATAA CCTCTGGTTCTTAC ACCTCTGGTTCTTACGTCTGTTGCTAGATTATCG
GT
FASLG NM_000639 881 GCACTTTGGGATTCT 882 GCATGTAAGAAGACCC 883 ACAACATTCTCGGT 884 GCACTTTGGGATTCTTTCCATTATGATTCTTTGTTACAG
TTCCATTAT TCACTGAA GCCTGTAACAAAGA GCACCGAGAATGTTGTATTCAGTGAGGGTCTTCTT
A
FASN NM_004104 885 GCCTCTTCCTGTTC 886 GCTTTGCCCGGTAGC 887 TCGCCCACCTACGT 888 GCCTCTTCCTGTTCGACGGCTCGCCCACCTACGTACT
ACTGGC
FCGR3A NM_000569 889 GTCTCCAGTGGAA 890 AGGAATGCAGCTACT 891 CCCATGATCTTCAA 892 GTCTCCAGTGGAAGGGAAAAGCCCATGATCTTCAAG
GCAGGG
FGF10 NM_004465 893 TCTTCCGTCCCTGT 894 AGAGTTGGTGGCCTC 895 ACACCATGTCCTGA 896 TCTTCCGTCCCTGTCACCTGCCAAGCCCTTGGTCAGG
CCAAGG
FGF17 NM_003867 897 GGTGGCTGTCCTC 898 TCTAGCCAGGAGGAG 899 TTCTCGGATCTCCC 900 GGTGGCTGTCCTCAAAATCTGCTTCTCGGATCTCCCT
TCAGTC
FGF5 NM_004464 901 GCATCGGTTTCCA 902 AACATATTGGCTTCGT 903 CCATTGACTTTGCC 904 GCATCGGTTTCCATCTGCAGATCTACCCGGATGGCAA
ATCCGG
FGF6 NM_020996 905 GGGCCATTAATTCTG 906 CCCGGGACATAGTGAT 907 CATCCACCTTGCCT 908 GGGCCATTAATTCTGACCACGTGCCTGAGAGGCAAGGTG
ACCAC GAA CTCAGGCAC GATGGCCCTGGGACAGAAACTGTTCATCATCTAT
FGF7 NM_002009 909 CCAGAGCAAATGGCT 910 TCCCCTCCTTCCATGT 911 CAGCCCTGAGCGAC 912 CCAGAGCAAATGGCTACAAATGTGAACTGTTCCAGCCCT
ACAAA AATC ACACAAGAAG GAGCGACACACAAGAAGTTATGATTACATGGAA
FGFR2 NM_000141 913 GAGGGACTGTTGGCA 914 GAGTGAGAATTCGATC 915 TCCCAGAGACCAAC 916 GAGGGACTGTTGGCATGCAGTGCCCTCCCAGAGACCAAC
TGCA CAAGTCTTC GTTCAAGCAGTTG GTTCAAGCAGTTGGTAGAAGACTTGGATCGAAT
FGFR4 NM_002011 917 CTGGCTTAAGGATGG 918 ACGAGACTCCAGTGCT 919 CCTTTCATGGGGAG 920 CTGGCTTAAGGATGGACAGGCCTTTCATGGGGAGAACCG
ACAGG GATG AACCGCATT CATTGGAGGCATTCGGCTGCGCCATCAGCACTG
FKBP5 NM_004117 921 CCCACAGTAGAGG 922 GGTTCTGGCTTTCACG 923 TCTCCCCAGTTCCA 924 CCCACAGTAGAGGGGTCTCATGTCTCCCCAGTTCCAC
CAGCAG
FLNA NM_001456 925 GAACCTGCGGTGG 926 GAAGACACCCTGGCC 927 TACCAGGCCCATAG 928 GAACCTGCGGTGGACACTTCCGGTGTCCAGTGCTAT
CACTGG
FLNC NM_001458 929 CAGGACAATGGTG 930 TGATGGTGTACTCGC 931 ATGTGCTGTCAGCT 932 CAGGACAATGGTGATGGCTCATGTGCTGTCAGCTAC
ACCTGC
FLT1 NM_002019 933 GGCTCCTGAATCT 934 TCCCACAGCAATACT 935 CTACAGCACCAAGA 936 GGCTCCTGAATCTATCTTTGACAAAATCTACAGCACC
GCGAC
FLT4 NM_002020 937 ACCAAGAAGCTGA 938 CCTGGAAGCTGTAGC 939 AGCCCGCTGACCAT 940 ACCAAGAAGCTGAGGACCTGTGGCTGAGCCCGCTGA
GGAAGA
FN1 NM_002026 941 GGAAGTGACAGAC 942 ACACGGTAGCCGGTC 943 ACTCTCAGGCGGTG 944 GGAAGTGACAGACGTGAAGGTCACCATCATGTGGAC
TCCACA
FOS NM_005252 945 CGAGCCCTTTGATGA 946 GGAGCGGGCTGTCTCA 947 TCCCAGCATCATCC 948 CGAGCCCTTTGATGACTTCCTGTTCCCAGCATCATCCAG
CTTCCT GA AGGCCCAG GCCCAGTGGCTCTGAGACAGCCCGCTCC
FOXO1 NM_002015 949 GTAAGCACCATGC 950 GGGGCAGAGGCACTT 951 TATGAACCGCCTGA 952 GTAAGCACCATGCCCCACACCTCGGGTATGAACCGC
CCCAAG
FOXP3 NM_014009 953 CTGTTTGCTGTCCG 954 GTGGAGGAACTCTGG 955 TGTTTCCATGGCTA 956 CTGTTTGCTGTCCGGAGGCACCTGTGGGGTAGCCAT
CCCCAC
FOXQ1 NM_033260 957 TGTTTTTGTCGCAA 958 TGGAAAGGTTCCCTG 959 TGATTTATGTCCCT 960 TGTTTTTGTCGCAACTTCCATTGATTTATGTCCCTTCC
TCCCTC
FSD1 NM_024333 961 AGGCCTCCTGTCC 962 TGTGTGAACCTGGTC 963 CGCACCAAACAAGT 964 AGGCCTCCTGTCCTTCTACAATGCCCGCACCAAACAA
GCTGCA
FYN NM_002037 965 GAAGCGCAGATCA 966 CTCCTCAGACACCAC 967 CTGAAGCACGACAA 968 GAAGCGCAGATCATGAAGAAGCTGAAGCACGACAAG
GCTGGT
G6PD NM_000402 969 AATCTGCCTGTGG 970 CGAGATGTTGCTGGT 971 CCAGCCTCAGTGCC 972 AATCTGCCTGTGGCCTTGCCCGCCAGCCTCAGTGCCA
ACTTGA
GABRG2 NM_198904 973 CCACTGTCCTGACAA 974 GAGATCCATCGCTGTG 975 CTCAGCACCATTGC 976 CCACTGTCCTGACAATGACCACCCTCAGCACCATTGCCC
TGACC ACAT CCGGAAAT GGAAATCGCTCCCCAAGGTCTCCTATGTCAGAGC
GADD45 NM_001924 977 GTGCTGGTGACGA 978 CCCGGCAAAAACAAA 979 TTCATCTCAATGGA 980 GTGCTGGTGACGAATCCACATTCATCTCAATGGAAG
AGGATC
GADD45 NM_015675 981 ACCCTCGACAAGA 982 TGGGAGTTCATGGGT 983 TGGGAGTTCATGGG 984 ACCCTCGACAAGACCACACTTTGGGACTTGGGAGCT
TACAGA
GDF15 NM_004864 985 CGCTCCAGACCTA 986 ACAGTGGAAGGACCA 987 TGTTAGCCAAAGAC 988 CGCTCCAGACCTATGATGACTTGTTAGCCAAAGACTG
TGCCAC
GHR NM_000163 989 CCACCTCCCACAG 990 GGTGCGTGCCTGTAG 991 CGTGCCTCAGCCTC 992 CCACCTCCCACAGGTTCAGGCGATTCCCGTGCCTCAG
CTGAGT
GNPTAB NM_024312 993 GGATTCACATCGC 994 GTTCTTGCATAACAAT 995 CCCTGCTCACATGC 996 GGATTCACATCGCGGAAAGTCCCTGCTCACATGCCTC
CTCACA
GNRH1 NM_000825 997 AAGGGCTAAATCCAG 998 CTGGATCTCTGTGGCT 999 TCCTGTCCTTCACT 1000 AAGGGCTAAATCCAGGTGTGACGGTATCTAATGATGTCC
GTGTG GGT GTCCTTGCCA TGTCCTTCACTGTCCTTGCCATCACCAGCCACAG
GPM6B NM_001001094 1001 ATGTGCTTGGAGTGG 1002 TGTAGAACATAAACAC 1003 CGCTGAGAAACCAA 1004 ATGTGCTTGGAGTGGCCTGGCTGGGTGTGTTTGGTTTCT
CCT GGGCA ACACACCCAG CAGCGGTGCCCGTGTTTATGTTCTACA
GPNMB NM_001005340 1005 CAGCCTCGCCTTTAA 1006 TGACAAATATGGCCAA 1007 CAAACAGTGCCCTG 1008 CAGCCTCGCCTTTAAGGATGGCAAACAGTGCCCTGATCT
GGAT GCAG ATCTCCGTTG CCGTTGGCTGCTTGGCCATATTTGTCA
GPR68 NM_003485 1009 CAAGGACCAGATC 1010 GGTAGGGCAGGAAGC 1011 CTCAGCACCGTGGT 1012 CAAGGACCAGATCCAGCGGCTGGTGCTCAGCACCGT
CATCTT
GPS1 NM_004127 1013 AGTACAAGCAGGC 1014 GCAGCTCAGGGAAGT 1015 CCTCCTGCTGGCTT 1016 AGTACAAGCAGGCTGCCAAGTGCCTCCTGCTGGCTT
CCTTTG
GRB7 NM_005310 1017 CCATCTGCATCCA 1018 GGCCACCAGGGTATT 1019 CTCCCCACCCTTGA 1020 CCATCTGCATCCATCTTGTTTGGGTCCCCACCCTTG
GAAGTG
GREM1 NM_013372 1021 GTGTGGGCAAGGA 1022 GACCTGATTTGGCCT 1023 TCCACCCTCCCTTT 1024 GTGTGGGCAAGGACAAGCAGGATAGTGGAGTGAGAA
CTCACT
GSK3B NM_002093 1025 GACAAGGACGGCA 1026 TTGTGGCCTGTCTGG 1027 CCAGGAGTTGCCAC 1028 GACAAGGACGGCAGCAAGGTGACAACAGTGGTGGCA
CACTGT
GSN NM_000177 1029 CTTCTGCTAAGCGGT 1030 GGCTCAAAGCCTTGCT 1031 ACCCAGCCAATCGG 1032 CTTCTGCTAAGCGGTACATCGAGACGGACCCAGCCAATC
ACATCGA TCAC GATCGGC GGGATCGGCGGACGCCCATACCGTGGTGAAGC
GSTM1 NM_000561 1033 AAGCTATGAGGAAAA 1034 GGCCCAGCTTGAATTT 1035 TCAGCCACTGGCTT 1036 AAGCTATGAGGAAAAGAAGTACACGATGGGGGACGCTCC
GAAGTACACGA TTCA CTGTCATAATCAGG TGATTATGACAGAAGCCAGTGGCTGAATGAAAA
AG
GSTM2 NM_000848 1037 CTGCAGGCACTCC 1038 CCAAGAAACCATGGC 1039 CTGAAGCTCTACTC 1040 CTGCAGGCACTCCCTGAAATGCTGAAGCTCTACTCAC
ACAGTT
HDAC1 NM_004964 1041 CAAGTACCACAGCGA 1042 GCTTGCTGTACTCCG 1043 TTCTTGCGCTCCAT 1044 CAAGTACCACAGCGATGACTACATTAAATTCTTGCGCTC
TGACTACATTA ACATGTT CCGTCCAGA CATCCGTCCAGATAACATGTCGGAGTACAGCAAG
HDAC9 NM_178423 1045 AACCAGGCAGTCACC 1046 CTCTGTCTTCCTGCA 1047 CCCCCTGAAGCTCT 1048 AACCAGGCAGTCACCTTGAGGAAGCAGAGGAAGAGCTTC
TTGAG TCGC TCCTCTGCTT AGGGGGACCAGGCGATGCAGGAAGACAGAG
HGD NM_000187 1049 CTCAGGTCTGCCC 1050 TTATTGGTGCTCCGT 1051 CTGAGCAGCTCTCA 1052 CTCAGGTCTGCCCCTACAATCTCTATGCTGAGCAGCT
G GGATCG
HIP1 NM_005338 1053 CTCAGAGCCCCAC 1054 GGGTTTCCCTGCCAT 1055 CGACTCACTGACCG 1056 CTCAGAGCCCCACCTGAGCCTGCCGACTCACTGACC
AGGCCT
HIRIP3 NM_003609 1057 GGATGAGGAAAAG 1058 TCCCTAGCTGACTTTC 1059 CCATTGCTCCTGGT 1060 GGATGAGGAAAAGGGGGATTGGAAACCCAGAACCAG
TCTGGG
HK1 NM_000188 1061 TACGCACAGAGGC 1062 GAGAGAAGTGCTGGA 1063 TAAGAGTCCGGGAT 1064 TACGCACAGAGGCAAGCAGCTAAGAGTCCGGGATCC
CCCCAG
HLA-G NM_002127 1065 CCATCCCCATCAT 1066 CCGCAGCTCCAGTGA 1067 CTGCAAGGACAACC 1068 CCTGCGCGGCTACTACAACCAGAGCGAGGCCAGTTC
AGGCC
HLF NM_002126 1069 CACCCTGCAGGTG 1070 GGTACCTAGGAGCAG 1071 TAAGTGATCTGCCC 1072 CACCCTGCAGGTGTCTGAGACTAAGTGATCTGCCCTC
TCCAGG
HNF1B NM_000458 1073 TCCCAGCATCTCA 1074 CGTACCAGGTGTACA 1075 CCCCTATGAAGACC 1076 TCCCAGCATCTCAACAAGGGCACCCCTATGAAGACC
CAGAAG
HPS1 NM_000195 1077 GCGGAAGCTGTAT 1078 TTCGGATAAGATGAC 1079 CAGTCACCAGCCCA 1080 GCGGAAGCTGTATGTGCTCAAGTACCTGTTTGAAGT
AAGTGC
HRAS NM_005343 1081 GGACGAATACGAC 1082 GCACGTCTCCCCATC 1083 ACCACCTGCTTCCG 1084 GGACGAATACGACCCCACTATAGAGGATTCCTACCG
GTAGGA
HSD17B10 NM_004493 1085 CCAGCGAGTTCTTGA 1086 ATCTCACCAGCCACCA 1087 TCATGGGCACCTTC 1088 CCACCAGACAAGACCGATTCGCTGGCCTCCATTTCTTCA
TGTGA GG AATGTGATCC ACCCAGTGCCTGTCATGAAACTTGTGG
HSD17B2 NM_002153 1089 GCTTTCCAAGTGG 1090 TGCCTGCGATATTTGT 1091 AGTTGCTTCCATCC 1092 GCTTTCCAAGTGGGGAATTAAAGTTGCTTCCATCCAA
AACCTG
HSD17B3 NM_000197 1093 GGGACGTCCTGGAAC 1094 TGGAGAATCTCACGCA 1095 CTTCATCCTCACAG 1096 GGGACGTCCTGGAACAGTTCTTCATCCTCACAGGGCTGC
AGT CTTC GGCTGCTGGT TGGTGTGCCTGGCCTGCCTGGCGAAGTGCGTGAG
HSD17B4 NM_000414 1097 CGGGAAGCTTCAG 1098 ACCTCAGGCCCAATA 1099 AGGCGGCGTCCTAT 1100 CGGGAAGCTTCAGAGTACCTTTGTATTTGAGGAAAT
TTCCTC
HSD3B2 NM_000198 1101 GCCTTCCTTTAACC 1102 GGAGTAAATTGGGCT 1103 ACTTCCAGCAGGAA 1104 GCCTTCCTTTAACCCTGATGTACTGGATTGGCTTCCT
GCCAAT
HSP90AB1 NM_007355 1105 GCATTGTGACCAGCA 1106 GAAGTGCCTGGGCTTT 1107 ATCCGCTCCATATT 1108 GCATTGTGACCAGCACCTACGGCTGGACAGCCAATATGG
CCTAC CAT GGCTGTCCAG AGCGGATCATGAAAGCCCAGGCACTTC
HSPA5 NM_005347 1109 GGCTAGTAGAACTGG 1110 GGTCTGCCCAAATGCT 1111 TAATTAGACCTAGG 1112 GGCTAGTAGAACTGGATCCCAACACCAAACTCTTAATTA
ATCCCAACA TTTC CCTCAGCTGCACTG GACCTAGGCCTCAGCTGCACTGCCCGAAAAGCA
C
HSPA8 NM_006597 1113 CCTCCCTCTGGTGGT 1114 GCTACATCTACACTTG 1115 CTCAGGGCCCACCA 1116 CCTCCCTCTGGTGGTGCTTCCTCAGGGCCCACCATTGAA
GCTT GTTGGCTTAA TTGAAGAGGTTG GAGGTTGATTAAGCCAACCAAGTGTAGATGTAGC
HSPB1 NM_001540 1117 CCGACTGGAGGAGCA 1118 ATGCTGGCTGACTCTG 1119 CGCACTTTTCTGAG 1120 CCGACTGGAGGAGCATAAAAGCGCAGCCGAGCCCAGCGC
TAAA CTC CAGACGTCCA CCCGCACTTTTCTGAGCAGACGTCCAGAGCAGA
HSPB2 NM_001541 1121 CACCACTCCAGAG 1122 TGGGACCAAACCATA 1123 CACCTTTCCCTTCC 1124 CACCACTCCAGAGGTAGCAGCATCCTTGGGGGAAGG
CCCAAG
HSPE1 NM_002157 1125 GCAAGCAACAGTAGT 1126 CCAACTTTCACGCTAA 1127 TCTCCACCCTTTCC 1128 GCAAGCAACAGTAGTCGCTGTTGGATCGGGTTCTAAAGG
CGCTG CTGGT TTTAGAACCCG AAAGGGTGGAGAGATTCAACCAGTTAGCGTGAA
HSPG2 NM_005529 1129 GAGTACGTGTGCC 1130 CTCAATGGTGACCAG 1131 CAGCTCCGTGCCTC 1132 GAGTACGTGTGCCGAGTGTTGGGCAGCTCCGTGCCT
TAGAGG
ICAM1 NM_000201 1133 GCAGACAGTGACCAT 1134 CTTCTGAGACCTCTGG 1135 CCGGCGCCCAACGT 1136 GCAGACAGTGACCATCTACAGCTTTCCGGCGCCCAACGT
CTACAGCTT CTTCGT GATTCT GATTCTGACGAAGCCAGAGGTCTCAGAAG
IER3 NM_003897 1137 GTACCTGGTGCGCGA 1138 GCGTCTCCGCTGTAGT 1139 TCAAGTTGCCTCGG 1140 GTACCTGGTGCGCGAGAGCGTATCCCCAACTGGGACTTC
GAG GTT AAGTCCCAGT CGAGGCAACTTGAACTCAGAACACTACAGCGGA
IFI30 NM_006332 1141 ATCCCATGAAGCC 1142 GCACCATTCTTAGTG 1143 AAAATTCCACCCCA 1144 ATCCCATGAAGCCCAGATACACAAAATTCCACCCCA
TGATCA
IFIT1 NM_001548 1145 TGACAACCAAGCA 1146 CAGTCTGCCCATGTG 1147 AAGTTGCCCCAGGT 1148 TGACAACCAAGCAAATGTGAGGAGTCTGGTGACCTG
CACCAG
IFNG NM_000619 1149 GCTAAAACAGGGAAG 1150 CAACCATTACTGGGAT 1151 TCGACCTCGAAACA 1152 GCTAAAACAGGGAAGCGAAAAAGGAGTCAGATGCTGTTT
CGAAA GCTC GCATCTGACTCC CGAGGTCGAAGAGCATCCCAGTAATGGTTG
IGF1 NM_000618 1153 TCCGGAGCTGTGA 1154 CGGACAGAGCGAGCT 1155 TGTATTGCGCACCC 1156 TCCGGAGCTGTGATCTAAGGAGGCTGGAGATGTATT
CTCAAG
IGF1R NM_000875 1157 GCATGGTAGCCGAAG 1158 TTTCCGGTAATAGTCT 1159 CGCGTCATACCAAA 1160 GCATGGTAGCCGAAGATTTCACAGTCAAAATCGGAGATT
ATTTCA GTCTCATAGATATC ATCTCCGATTTTGA TTGGTATGACGCGAGATATCTATGAGACAGACTA
IGF2 NM_000612 1161 CCGTGCTTCCGGA 1162 TGGACTGCTTCCAGG 1163 TACCCCGTGGGCAA 1164 CCGTGCTTCCGGACAACTTCCCCAGATACCCCGTGGG
GTTCTT
IGFBP2 NM_000597 1165 GTGGACAGCACCA 1166 CCTTCATACCCGACTT 1167 CTTCCGGCCAGCAC 1168 GTGGACAGCACCATGAACATGTTGGGCGGGGGAGGC
TGCCTC
IGFBP3 NM_000598 1169 ACATCCCAACGCA 1170 CCACGCCCTTGTTTCA 1171 ACACCACAGAAGGC 1172 ACATCCCAACGCATGCTCCTGGAGCTCACAGCCTTCT
TGTGA
IGFBP5 NM_000599 1173 TGGACAAGTACGG 1174 CGAAGGTGTGGCACT 1175 CCCGTCAACGTACT 1176 TGGACAAGTACGGGATGAAGCTGCCAGGCATGGAGT
CCATGC
IGFBP6 NM_002178 1177 TGAACCGCAGAGACC 1178 GTCTTGGACACCCGCA 1179 ATCCAGGCACCTCT 1180 TGAACCGCAGAGACCAACAGAGGAATCCAGGCACCTCTA
AACAG GAAT ACCACGCCCTC CCACGCCCTCCCAGCCCAATTCTGCGGGTGTCCA
IL10 NM_000572 1181 CTGACCACGCTTT 1182 CCAAGCCCAGAGACA 1183 TTGAGCTGTTTTCC 1184 CTGACCACGCTTTCTAGCTGTTGAGCTGTTTTCCCTG
CTGACC
IL11 NM_000641 1185 TGGAAGGTTCCAC 1186 TCTTGACCTTGCAGCT 1187 CCTGTGATCAACAG 1188 TGGAAGGTTCCACAAGTCACCCTGTGATCAACAGTA
TACCCG
IL17A NM_002190 1189 TCAAGCAACACTC 1190 CAGCTCCTTTCTGGGT 1191 TGGCTTCTGTCTGA 1192 TCAAGCAACACTCCTAGGGCCTGGCTTCTGTCTGATC
TCAAGG
IL1A NM_000575 1193 GGTCCTTGGTAGA 1194 GGATGGAGCTTCAGG 1195 TCTCCACCCTGGCC 1196 GGTCCTTGGTAGAGGGCTACTTTACTGTAACAGGGC
CTGTTA
IL1B NM_000576 1197 AGCTGAGGAAGAT 1198 GGAAAGAAGGTGCTC 1199 TGCCCACAGACCTT 1200 AGCTGAGGAAGATGCTGGTTCCCTGCCCACAGACCT
CCAGGA
IL2 NM_000586 1201 ACCTCAACTCCTGCC 1202 CACTGTTTGTGACAAG 1203 TGCAACTCCTGTCT 1204 ACCTCAACTCCTGCCACAATGTACAGGATGCAACTCCTG
ACAAT TGCAAG TGCATTGCAC TCTTGCATTGCACTAAGTCTTGCACTTGTCACAAA
IL6 NM_000600 1205 CCTGAACCTTCCA 1206 ACCAGGCAAGTCTCC 1207 CCAGATTGGAAGCA 1208 CCTGAACCTTCCAAAGATGGCTGAAAAAGATGGATG
TCCATC
IL6R NM_000565 1209 CCAGCTTATCTCA 1210 CTGGCGTAGAACCTT 1211 CCTTTGGCTTCACG 1212 CCAGCTTATCTCAGGGGTGTGCGGCCTTTGGCTTCAC
GAAGAG
IL6ST NM_002184 1213 GGCCTAATGTTCC 1214 AAAATTGTGCCTTGG 1215 CATATTGCCCAGTG 1216 GGCCTAATGTTCCAGATCCTTCAAAGAGTCATATTGC
GTCACC
IL8 NM_000584 1217 AAGGAACCATCTCAC 1218 ATCAGGAAGGCTGCCA 1219 TGACTTCCAAGCTG 1220 AAGGAACCATCTCACTGTGTGTAAACATGACTTCCAAGC
TGTGTGTAAAC AGAG GCCGTGGC TGGCCGTGGCTCTCTTGGCAGCCTTCCTGAT
ILF3 NM_004516 1221 GACACGCCAAGTG 1222 CTCAAGACCCGGATC 1223 ACACAAGACTTCAG 1224 GACACGCCAAGTGGTTCCAGGCCAGAGCCAACGGGC
CCCGTT
ILK NM_001014794 1225 CTCAGGATTTTCTCG 1226 AGGAGCAGGTGGAGAC 1227 ATGTGCTCCCAGTG 1228 CTCAGGATTTTCTCGCATCCAAATGTGCTCCCAGTGCTA
CATCC TGG CTAGGTGCCT GGTGCCTGCCAGTCTCCACCTGCTCCT
IMMT NM_006839 1229 CTGCCTATGCCAG 1230 GCTTTTCTGGCTTCCT 1231 CAACTGCATGGCTC 1232 CTGCCTATGCCAGACTCAGAGGAATCGAACAGGCTG
TGAACA
ING5 NM_032329 1233 CCTACAGCAAGTG 1234 CATCTCGTAGGTCTG 1235 CCAGCTGCACTTTG 1236 CCTACAGCAAGTGCAAGGAATACAGTGACGACAAAG
TCGTCA
INHBA NM_002192 1237 GTGCCCGAGCCAT 1238 CGGTAGTGGTTGATG 1239 ACGTCCGGGTCCTC 1240 GTGCCCGAGCCATATAGCAGGCACGTCCGGGTCCTC
ACTGTC
INSL4 NM_002195 1241 CTGTCATATTGCCC 1242 CAGATTCCAGCAGCC 1243 TGAGAAGACATTCA 1244 CTGTCATATTGCCCCATGCCTGAGAAGACATTCACCA
CCACCA
ITGA1 NM_181501 1245 GCTTCTTCTGGAG 1246 CCTGTAGATAATGAC 1247 TTGCTGGACAGCCT 1248 GCTTCTTCTGGAGATGTGCTCTATATTGCTGGACAGC
CGGTAC
ITGA3 NM_002204 1249 CCATGATCCTCAC 1250 GAAGCTTTGTAGCCG 1251 CACTCCAGACCTCG 1252 CCATGATCCTCACTCTGCTGGTGGACTATACACACTCCA
CTTAGC
ITGA4 NM_000885 1253 CAACGCTTCAGTG 1254 GTCTGGCCGGGATTC 1255 CGATCCTGCATCTG 1256 CAACGCTTCAGTGATCAATCCCGGGGCGATTTACAG
TAAATC
ITGA5 NM_002205 1257 AGGCCAGCCCTAC 1258 GTCTTCTCCACAGTCC 1259 TCTGAGCCTTGTCC 1260 AGGCCAGCCCTACATTATCAGAGCAAGAGCCGGATA
TCTATC
ITGA6 NM_000210 1261 CAGTGACAAACAG 1262 GTTTAGCCTCATGGG 1263 TCGCCATCTTTTGT 1264 CAGTGACAAACAGCCCTTCCAACCCAAGGAATCCCA
GGGATT
ITGA7 NM_002206 1265 GATATGATTGGTCGC 1266 AGAACTTCCATTCCCC 1267 CAGCCAGGACCTGG 1268 GATATGATTGGTCGCTGCTTTGTGCTCAGCCAGGACCTG
TGCTTTG ACCAT CCATCCG GCCATCCGGGATGAGTTGGATGGTGGGGAATGGA
ITGAD NM_005353 1269 GAGCCTGGTGGAT 1270 ACTGTCAGGATGCCC 1271 CAACTGAAAGGCCT 1272 GAGCCTGGTGGATCCCATCGTCCAACTGAAAGGCCT
GACGTT
ITGB3 NM_000212 1273 ACCGGGAGCCCTACA 1274 CCTTAAGCTCTTTCAC 1275 AAATACCTGCAACC 1276 ACCGGGGAGCCCTACATGACGAAAATACCTGCAACCGTT
TGAC TGACTCAATCT GTTACTGCCGTGAC ACTGCCGTGACGAGATTGAGTCAGTGAAAGAGC
ITGB4 NM_000213 1277 CAAGGTGCCCTCA 1278 GCGCACACCTTCATC 1279 CACCAACCTGTACC 1280 CAAGGTGCCCTCAGTGGAGCTCACCAACCTGTACCC
CGTATT
ITGB5 NM_002213 1281 TCGTGAAAGATGA 1282 GGTGAACATCATGAC 1283 TGCTATGTTTCTAC 1284 TCGTGAAAGATGACCAGGAGGCTGTGCTATGTTTCTA
AAAACC
ITPR1 NM_002222 1285 GAGGAGGTGTGGG 1286 GTAATCCCATGTCCG 1287 CCATCCTAACGGAA 1288 GAGGAGGTGTGGGTGTTCCGCTTCCATCCTAACGGA
CGAGCT
ITPR3 NM_002224 1289 TTGCCATCGTGTC 1290 ATGGAGCTGGCGTCA 1291 TCCAGGTCTCGGAT 1292 TTGCCATCGTGTCAGTGCCCGTGTCTGAGATCCGAGA
CTCAGA
ITSN1 NM_003024 1293 TAACTGGGATGCA 1294 CTCTGCCTTAACTGGC 1295 AGCCCTCTCTCACC 1296 TAACTGGGATGCATGGGCAGCCCAGCCCTCTCTCAC
GTTCCA
JAG1 NM_000214 1297 TGGCTTACACTGG 1298 GCATAGCTGTGAGAT 1299 ACTCGATTTCCCAG 1300 TGGCTTACACTGGCAATGGTAGTTTCTGTGGTTGGCT
CCAACC
JUN NM_002228 1301 GACTGCAAAGATGGA 1302 TAGCCATAAGGTCCGC 1303 CTATGACGATGCCC 1304 GACTGCAAAGATGGAAACGACCTTCTATGACGATGCCCT
AACGA TCTC TCAACGCCTC CAACGCCTCGTTCCTCCCGTCCGAGAGCGGACCT
JUNB NM_002229 1305 CTGTCAGCTGCTG 1306 AGGGGGTGTCCGTAA 1307 CAAGGGACACGCCT 1308 CTGTCAGCTGCTGCTTGGGGTCAAGGGACACGCCTT
TCTGAA
KCNN2 NM_021614 1309 TGTGCTATTCATCC 1310 GGGCATAGGAGAAGG 1311 TTATACATTCACAT 1312 TGTGCTATTCATCCCATACCTGGGAATTATACATTCA
GGACGG
KCTD12 NM_138444 1313 AGCAGTTACTGGC 1314 TGGAGACCTGAGCAG 1315 ACTCTTAGGCGGCA 1316 AGCAGTTACTGGCAAGAGGGAGAAAGGACGCTGCCG
GCGTCC
KHDRBS NM_006558 1317 CGGGCAAGAAGAG 1318 CTGTAGACGCCCTTT 1319 CAAGACACAAGGCA 1320 CGGGCAAGAAGAGTGGACTAACTCAAGACACAAGGC
CCTTCA
KIAA019 NM_014846 1321 CAGACACCAGCTC 1322 AACATTGTGAGGCGG 1323 TCCCCAGTGTCCAG 1324 CAGACACCAGCTCTGAGGCCAGTTAATCATCCCCAG
GCACAG
KIAA024 NM_014734 1325 CCGTGGGACATGG 1326 GAAGCAAGTCCGTCT 1327 TCCGCTAGTGATCC 1328 CCGTGGGACATGGAGTGTTCCTTCCGCTAGTGATCCT
TTTGCA
KIF4A NM_012310 1329 AGAGCTGTCTCC 1330 GCTGGTCTTGCTCTGT 1331 CAGGTCAGCAAACT 1332 AGAGCTGGTCTCCTCCAAAATACAGGTCAGCAAACT
TGAAAG
KIT NM_000222 1333 GAGGCAACTGCTTAT 1334 GGCACTCGGCTTGAGC 1335 TTACAGCGACAGTC 1336 GAGGCAACTGCTTATGGCTTAATTAAGTCAGATGCGGCC
GGCTTAATTA AT ATGGCCGCAT ATGACTGTCGCTGTAAAGATGCTCAAGCCGAGT
KLC1 NM_182923 1337 AGTGGCTACGGGA 1338 TGAGCCACAGACTGC 1339 CAACACGCAGCAGA 1340 AGTGGCTACGGGATGAACTGGCCAACACGCAGCAGA
AACTG
KLF6 NM_001300 1341 CACGAGACCGGCT 1342 GCTCTAGGCAGGTCT 1343 AGTACTCCTCCAGA 1344 CACGAGACCGGCTACTTCTCGGCGCTGCCGTCTCTGG
GACGGC
KLK1 NM_002257 1345 AACACAGCCCAGTTT 1346 CCAGGAGGCTCATGTT 1347 TCAGTGAGAGCTTC 1348 AACACAGCCCAGTTTGTTCATGTCAGTGAGAGCTTCCCA
GTTCA GAAG CCACACCCTG CACCCTGGCTTCAACATGAGCCTCCTGG
KLK10 NM_002776 1349 GCCCAGAGGCTCC 1350 CAGAGGTTTGAACAG 1351 CCTCTTCCTCCCCA 1352 GCCCAGAGGCTCCATCGTCCATCCTCTTCCTCCCCAG
GTCGGC
KLK11 NM_006853 1353 CACCCCGGCTTCA 1354 CATCTTCACCAGCAT 1355 CCTCCCCAACAAAG 1356 CACCCCGGCTTCAACAACAGCCTCCCCAACAAAGAC
ACCACC
KLK14 NM_022046 1357 CCCCTAAAATGTT 1358 CTCATCCTCTTGGCTC 1359 CAGCACTTCAAGTC 1360 CCCCTAAAATGTTCCTCCTGCTGACAGCACTTCAAGT
CTGGCT
KLK2 NM_005551 1361 AGTCTCGGATTGT 1362 TGTACACAGCCACCT 1363 TTGGGAATGCTTCT 1364 AGTCTCGGATTGTGGGAGGCTGGGAGTGTGAGAAGC
CACACT
KLK3 NM_001648 1365 CCAAGCTTACCAC 1366 AGGGTGAGGAAGACA 1367 ACCCACATGGTGAC 1368 CCAAGCTTACCACCTGCACCCGGAGAGCTGTGTCAC
ACAGCT
KLRK1 NM_007360 1369 TGAGAGCCAGGCT 1370 ATCCTGGTCCTCTTTG 1371 TGTCTCAAAATGCC 1372 TGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGC
AGCCTT
KPNA2 NM_002266 1373 TGATGGTCCAAAT 1374 AAGCTTCACAAGTTG 1375 ACTCCTGTTTTCAC 1376 TGATGGTCCAAATGAACGAATTGGCATGGTGGTGAA
CACCAT
KRT1 NM_006121 1377 TGGACAACAACCG 1378 TATCCTCGTACTGGG 1379 CCTCAGCAATGATG 1380 TGGACAACAACCGCAGTCTCGACCTGGACAGCATCA
CTGTCC
KRT15 NM_002275 1381 GCCTGGTTCTTCA 1382 CTTGCTGGTCTGGATC 1383 TGAACAAAGAGGTG 1384 GCCTGGTTCTTCAGCAAGACTGAGGAGCTGAACAAA
GCCTCC
KRT18 NM_000224 1385 AGAGATCGAGGCT 1386 GGCCTTTTACTTCCTC 1387 TGGTTCTTCTTCAT 1388 AGAGATCGAGGCTCTCAAGGAGGAGCTGCTCTTCAT
GAAGAG
KRT2 NM_000423 1389 CCAGTGACGCCTC 1390 GGGCATGGCTAGAAG 1391 ACCTAGACAGCACA 1392 CCAGTGACGCCTCTGTGTTCTGGGGCGGAATCTGTGC
GATTCC
KRT5 NM_000424 1393 TCAGTGGAGAAGG 1394 TGCCATATCCAGAGG 1395 CCAGTCAACATCTC 1396 TCAGTGGAGAAGGAGTTGGACCAGTCAACATCTCTG
TGTTGT
KRT75 NM_004693 1397 TCAAAGTCAGGTACG 1398 ACGCTCCTTTTTCAGG 1399 TTCATTCTCAGCAG 1400 TCAAAGTCAGGTACGAAGATGAAATTAACAAGCGCACAG
AAGATGAAATT GCTACAA CTGTGCGCTTGT CTGCTGAGAATGAATTTGTAGCCCTGAAAAAGG
KRT76 NM_015848 1401 ATCTCCAGACTGCTG 1402 TCAGGGAATTAGGGGA 1403 TCTGGGCTTCAGAT 1404 ATCTCCAGACTGCTGGTTCCCAGGGAACCCTCCCTACAT
GTTCC CAGA CCTGACTCCC CTGGGCTTCAGATCCTGACTCCCTTCTGTCCCCTA
KRT8 NM_002273 1405 GGATGAAGCTTACAT 1406 CATATAGCTGCCTGAG 1407 CGTCGGTCAGCCCT 1408 GGATGAAGCTTACATGAACAAGGTAGAGCTGGAGTCTCG
GAACAAGGTAG GAAGTTGAT TCCAGGC CCTGGAAGGGCTGACCGACGAGATCAACTTCCT
L1CAM NM_000425 1409 CTTGCTGGCCAAT 1410 TGATTGTCCGCAGTC 1411 ATCTACGTTGTCCA 1412 CTTGCTGGCCAATGCCTACATCTACGTTGTCCAGCTG
GCTGCC
LAG3 NM_002286 1413 GCCTTAGAGCAAG 1414 CGGTTCTTGCTCCAGC 1415 TCTATCTTGCTCTG 1416 GCCTTAGAGCAAGGGATTCACCCTCCGCAGGCTCAG
AGCCTG
LAMA3 NM_000227 1417 CCTGTCACTGAAG 1418 TGGGTTACTGGTCAG 1419 ATTCAGACTGACAG 1420 CCTGTCACTGAAGCCTTGGAAGTCCAGGGGCCTGTC
GCCCCT
LAMA4 NM_002290 1421 GATGCACTGCGGT 1422 CAGAGGATACGCTCA 1423 CTCTCCATCGAGGA 1424 GATGCACTGCGGTTAGCAGCGCTCTCCATCGAGGAA
AGGCAA
LAMA5 NM_005560 1425 CTCCTGGCCAACA 1426 ACACAAGGCCCAGCC 1427 CTGTTCCTGGAGCA 1428 CTCCTGGCCAACAGCACTGCACTAGAAGAGGCCATG
TGGCCT
LAMB1 NM_002291 1429 CAAGGAGACTGGG 1430 CGGCAGAACTGACAG 1431 CAAGTGCCTGTACC 1432 CAAGGAGACTGGGAGGTGTCTCAAGTGCCTGTACCA
ACACGG
LABM3 NM_000228 1433 ACTGACCAAGCCT 1434 GTCACACTTGCAGCA 1435 CCACTCGCCATACT 1436 ACTGACCAAGCCTGAGACCTACTGCACCCAGTATGG
GGGTGC
LAMC1 NM_002293 1437 GCCGTGATCTCAG 1438 ACCTGCTTGCCCAAG 1439 CCTCGGTACTTCAT 1440 GCCGTGATCTCAGACAGCTACTTTCCTCGGTACTTCA
TGCTCC
LAMC2 NM_005562 1441 ACTCAAGCGGAAATT 1442 ACTCCCTGAAGCCGAG 1443 AGGTCTTATCAGCA 1444 ACTCAAGCGGAAATTGAAGCAGATAGGTCTTATCAGCAC
GAAGCA ACACT CAGTCTCCGCCTCC AGTCTCCGCCTCCTGGATTCAGTGTCTCGGCTTC
LAPTM5 NM_006762 1445 TGCTGGACTTCTG 1446 TGAGATAGGTGGGCA 1447 TCCTGACCCTCTGC 1448 TGCTGGACTTCTGCCTGAGCATCCTGACCCTCTGCAG
AGCTCC
LGALS3 NM_002306 1449 AGCGGAAAATGGC 1450 CTTGAGGGTTTGGGT 1451 ACCCAGATAACGCA 1452 AGCGGAAAATGGCAGACAATTTTTCGCTCCATGATG
TCATGG
LIG3 NM_002311 1453 GGAGGTGGAGAAG 1454 ACAGGTGTCATAGC 1455 CTGGACGCTCAGAG 1456 GGAGGTGGAGAAGGAGCCGGGCCAGAGACGAGCTCT
CTCGTC
LIMS1 NM_004987 1457 TGAACAGTAATGG 1458 TTCTGGGAACTGCTG 1459 ACTGAGCGCACACG 1460 TGAACAGTAATGGGGAGCTGTACCATGAGCAGTGTT
AAACA
LOX NM_002317 1461 CCAATGGGAGAAC 1462 CGCTGAGGCTGGTAC 1463 CAGGCTCAGCAAGC 1464 CCAATGGGAGAACAACGGGCAGGTGTTCAGCTTGCT
TGAACA
LRP1 NM_002332 1465 TTTGGCCCAATGGGC 1466 GTCTCGATGCGGTCGT 1467 TCCCGGCTGGGCGC 1468 TTTGGCCCAATGGGCTAAGCCTGGACATCCCGGCTGGGC
TAAG AGAAG CTCTACT GCCTCTACTGGGTGGATGCCTTCTACGACCGCAT
LTBP2 NM_000428 1469 GCACACCCATCCT 1470 GATGGCTGGCCACGT 1471 CTTTGCAGCCCTCA 1472 GCACACCCATCCTTGAGTCTCCTTTGCAGCCCTCAGA
GAACTC
LUM NM_002345 1473 GGCTCTTTTGAAGGA 1474 AAAAGCAGCTGAAACA 1475 CCTGACCTTCATCC 1476 GGCTCTTTTGAAGGATTGGTAAACCTGACCTTCATCCAT
TTGGTAA GCATC ATCTCCAGCA CTCCAGCACAATCGGCTGAAAGAGGATGCTGTTT
MAGEA4 NM_002362 1477 GCATCTAACAGCC 1478 CAGAGTGAAGAATGG 1479 CAGCTTCCCTTGCC 1480 GCATCTAACAGCCCTGTGCAGCAGCTTCCCTTGCCTC
TCGTGT
MANF NM_006010 1481 CAGATGTGAAGCC 1482 AAGGGAATCCCCTCA 1483 TTCCTGATGATGCT 1484 CAGATGTGAAGCCTGGAGCTTTCCTGATGATGCTGG
GGCCCT
MAOA NM_000240 1485 GTGTCAGCCAAAG 1486 CGACTACGTCGAACA 1487 CCGCGATACTCGCC 1488 GTGTCAGCCAAAGCATGGAGAATCAAGAGAAGGCGA
TTCTCT
MAP3K5 NM_005923 1489 AGGACCAAGAGGC 1490 CCTGTGGCCATTTCA 1491 CAGCCCAGAGACCA 1492 AGGACCAAGAGGCTACGGAAAAGCAGCAGACATCTG
GATGTC
MAP3K7 NM_145333 1493 CAGGCAAGAACTAGT 1494 CCTGTACCAGGCGAGA 1495 TGCTGGTCCTTTTC 1496 CAGGCAAGAACTAGTTGCAGAACTGGACCAGGATGAAAA
TGCAGAA TGTAT ATCCTGGTCC GGACCAGCAAAATACATCTCGCCTGGTACAGG
MAP4K4 NM_004834 1497 TCGCCGAGATTTC 1498 CTGTTGTCTCCGAAG 1499 AACGTTCCTTGTTC 1500 TCGCCGAGATTTCCTGAGACTGCAGCAGGAGAACAA
TCCTGC
MAP7 NM_003980 1501 GAGGAACAGAGGT 1502 CTGCCAACTGGCTTTC 1503 CATGTACAACAAAC 1504 GAGGAACAGAGGTGTCTGCACTTCCATGTACAACAA
GCTCCG
MAPKAPK3 NM_004635 1505 AAGCTGCAGAGATAA 1506 GTGGGCAATGTTATGG 1507 ATTGGCACTGCCAT 1508 AAGCTGCAGAGATAATGCGGGATATTGGCACTGCCATCC
TGCGG CTG CCAGTTTCTG AGTTTCTGCACAGCCATAACATTGCCCAC
MCM2 NM_004526 1509 GACTTTTGCCCGCTA 1510 GCCACTAACTGCTTCA 1511 ACAGCTCATTGTTG 1512 GACTTTTGCCCGCTACCTTTCATTCCGCGTGACAACAAT
CCTTTC GTATGAAGAG TCACGCCGGA GAGCTGTTGCTCTTCATACTGAAGCAGTTAGTGG
MCM3 NM_002388 1513 GGAGAACAATCCC 1514 ATCTCCTGGATGGTG 1515 TGGCCTTTCTGTCT 1516 GGAGAACAATCCCCTTGAGACAGAATATGGCCTTTC
ACAAGG
MCM6 NM_005915 1517 TGATGGTCCTATGTG 1518 TGGGACAGGAAACACA 1519 CAGGTTTCATACCA 1520 TGATGGTCCTATGTGTCACATTCATCACAGGTTTCATAC
TCACATTCA CCAA ACACAGGCTTCAGC CAACACAGGCTTCAGCACTTCCTTTGGTGTGTTTC
MDK NM_002391 1521 GGAGCCGACGTGCA 1522 GACTTTGGTGCCTGT 1523 ATCACACGCACCCC 1524 GGAGCCGACTGCAAGTACAAGTTTGAGAACTGGGGT
AGTTCT
MDM2 NM_002392 1525 CTACAGGGACGCC 1526 ATCCAACCAATCACC 1527 CTTACACCAGCATC 1528 CTACAGGGACGCCATCGAATCCGGATCTTGATGCTG
AAGATC
MELK NM_014791 1529 AGGATCGCCTGTC 1530 TGCACATAAGCAACA 1531 CCCGGGTTGTCTTC 1532 AGGATCGCCTGTCAGAAGAGGAGACCCGGGTTGTCT
CGTCAG
MET NM_000245 1533 GACATTTCCAGTCCT 1534 CTCCGATCGCACACAT 1535 TGCCTCTCTGCCCC 1536 GACATTTCCAGTCCTGCAGTCAATGCCTCTCTGCCCCAC
GCAGTCA TTGT ACCCTTTGT CCTTTGTTCAGTGTGGCTGGTGCCACGACAAATGT
MGMT NM_002412 1537 GTGAAATGAAACG 1538 GACCCTGCTCACAAC 1539 CAGCCCTTTGGGGA 1540 GTGAAATGAAACGCACCACACTGGACAGCCCTTTGG
AGCTGG
MGST1 NM_020300 1541 ACGGATCTACCACAC 1542 TCCATATCCAACAAAA 1543 TTTGACACCCCTTC 1544 ACGGATCTACCACACCATTGCATATTTGACACCCCTTCC
CATTGC AAACTCAAAG CCCAGCCA CCAGCCAAATAGAGCTTTGAGTTTTTTTGTTGGAT
MICA NM_000247 1545 ATGGTGAATGTCA 1546 AAGCCAGAAGCCCTG 1547 CGAGGCCTCAGAGG 1548 ATGGTGAATGTCACCCGCAGCGAGGCCTCAGAGGGC
GCAAC
MKI67 NM_002417 1549 GATTGCACCAGGG 1550 TCCAAAGTGCCTCTG 1551 CCACTCTTCCTTGA 1552 GATTGCACCAGGGCAGAACAGGGGAGGGTGTTCAAG
ACACCC
MLXIP NM_014938 1553 TGCTTAGCTGGCA 1554 CAGCCTACTCTCCAT 1555 CATGAGATGCCAGG 1556 TGCTTAGCTGGCATGTGGCCGCATGAGATGCCAGGA
AGACCC
MMP11 NM_005940 1557 CCTGGAGGCTGCAAC 1558 TACAATGGCTTTGGAG 1559 ATCCTCCTGAAGCC 1560 CCTGGAGGCTGCAACATACCTCAATCCTGTCCCAGGCCG
ATACC GATAGCA CTTTTCGCAGC GATCCTCCTGAAGCCCTTTTCGCAGCACTGCTAT
MMP2 NM_004530 1561 CAGCCAGAAGCGG 1562 AGACACCATCACCTG 1563 AAGTCCGAATCTCT 1564 CAGCCAGAAGCGGAAACCTTAAAAAGTCCGATCTCT
GCTCCC
MMP7 NM_002423 1565 GGATGGTAGCAGTCT 1566 GGAATGTCCCATACCC 1567 CCTGTATGCTGCAA 1568 GGATGGTAGCAGTCTAGGGATTAACTTCCTGTATGCTGC
AGGGATTAACT AAAGAA CTCATGAACTTGGC AACTCATGAACTTGGCCATTCTTTGGGTATGGGAC
MMP9 NM_004994 1569 GAGAACCAATCTC 1570 CACCCGAGTGTAACC 1571 ACAGGTATTCCTCT 1572 GAGAACCAATCTCACCGACAGGCAGCTGGCAGAGGA
GCCAGC
MPPED2 NM_001584 1573 CCGACCAACCCTC 1574 AGGGCATTTAGAGCT 1575 ATTTGACCTTCCAA 1576 CCGACCAACCCTCCAATTATATTTGACCTTCCAAACC
ACCCAC
MRC1 NM_002438 1577 CTTGACCTCAGGA 1578 GGACTGCGGTCACTC 1579 CCAACCGCTGTTGA 1580 CTTGACCTCAGGACTCTGGATTGGACTTAACAGTCTG
AGCTCA
MRPL13 NM_014078 1581 TCCGGTTCCCTTCG 1582 GTGGAAAAACTGCGG 1583 CGGCTGGAAATTAT 1584 TCCGGTTCCCTTCGTTTAGGTCGGCTGGAAATTATGT
GTCCTC
MSH2 NM_000251 1585 GATGCAGAATTGA 1586 TCTTGGCAAGTCGGT 1587 CAAGAAGATTTACT 1588 GATGCAGAATTGAGGCAGACTTTACAAGAAGATTTA
TCGTCG
MSH3 NM_002439 1589 TGATTACCATCATGG 1590 CTTGTGAAAATGCCAT 1591 TCCCAATTGTCGCT 1592 TGATTACCATCATGGCTCAGATTGGCTCCTATGTTCCTG
CTCAGA CCAC TCTTCTGCAG CAGAAGAAGCGACAATTGGGATTGTGGATGGCAT
MSH6 NM_000179 1593 TCTATTGGGGGAT 1594 CAAATTGCGAGTGGT 1595 CCGTTACCAGCTGG 1596 TCTATTGGGGGATTGGTAGGAACCGTTACCAGCTGG
AAATTC
MTA1 NM_004689 1597 CCGCCCTCACCTGAA 1598 GGAATAAGTTAGCCGC 1599 CCCAGTGTCCGCCA 1600 CCGCCCTCACCTGCAGAGAAACGCGCTCCTTGGCGGACA
GAGA GCTTCT AGGAGCG CTGGGGGAGGAGAGGAAGAAGCGCGGCTAACTT
MTPN NM_145808 1601 GGTGGAAGGAAAC 1602 CAGCAGCAGAAATTC 1603 AAGCTGCCCACAAT 1604 GGTGGAAGGAAACCTCTTCATTATGCAGCAGATTGT
CTGCTG
MTSS1 NM_014751 1605 TTCGACAAGTCCT 1606 CTTGGAACATCCGTC 1607 CCAAGAAACAGCGA 1608 TTCGACAAGTCCTCCACCATTCCAAGAAACAGCGAC
CATCA
MUC1 NM_002456 1609 GGCCAGGATCTGTGG 1610 CTCCACGTCGTGGACA 1611 CTCTGGCCTTCCGA 1612 GGCCAGGATCTGTGGTGGTACAATTGACTCTGGCCTTCC
TGGTA TTGA GAAGGTACC GAGAAGGTACCATCAATGTCCACGACGTGGAG
MVP NM_017458 1613 ACGAGAACGAGGGCA 1614 GCATGTAGGTGCTTCC 1615 CGCACCTTTCCGGT 1616 ACGAGAACGAGGGCATCTATGTGCAGGATGTCAAGACCG
TCTATGT AATCAC CTTGACATCCT GAAAGGTGCGCGCTGTGATTGGAAGCACCTACA
MYBL2 NM_002466 1617 GCCGAGATCGCCAAG 1618 CTTTTGATGGTAGAGT 1619 CAGCATTGTCTGTC 1620 GCCGAGATCGCCAAGATGTTGCCAGGGAGGACAGACAAT
ATG TCCAGTGATTC CTCCCTGGCA GCTGTGAAGAATCACTGGAACTCTACCATCAAA
MYBPC1 NM_002465 1621 CAGCAACCAGGGA 1622 CAGCAGTAAGTGCCT 1623 AAATTCGCAAGCCC 1624 CAGCAACCAGGGAGTCTGTACCCTGGAAATTCGCAA
AGCCCC
MYC NM_002467 1625 TCCCTCCACTCGGAA 1626 CGGTTGTTGCTGATCT 1627 TCTGACACTGTCCA 1628 TCCCTCCACTCGGAAGGACTATCCTGCTGCCAAGAGGGT
GGACTA GTCTCA ACTTGACCCTCTT CAAGTTGGACAGTGTCAGAGTCCTGAGACAGAT
MYLK3 NM_182493 1629 CACCTGACTGAGCTG 1630 GATGTAGTGCTGGTGC 1631 CACACCCTCACAGA 1632 CACCTGACTGAGCTGGATGTGGTCCTGTTCACCAGGCAG
GATGT AGGT TCTGCCTGGT ATCTGTGAGGGTGTGCATTACCTGCACCAGCACT
MYO6 NM_004999 1633 AAGCAGTTCTGGA 1634 GATGAGCTCGGCTTC 1635 CAATCCTCAGGGCC 1636 AAGCAGTTCTGGAGCAGGAGCGCAGGGACCGGGAGC
AGCTCC
NCAM1 NM_000615 1637 TAGTTCCCAGCTG 1638 CAGCCTTGTTCTCAGC 1639 CTCAGCCTCGTCGT 1640 TAGTTCCCAGCTGACCATCAAAAAGGTGGATAAGAA
TCTTAT
NCAPD3 NM_015261 1641 TCGTTGCTTAGAC 1642 CTCCAGACAGTGTGC 1643 CTACTGTCCGCAGC 1644 TCGTTGCTTAGACAAGGCGCCTACTGTCCGCAGCAA
AAGGCA
NCOR1 NM_006311 1645 AACCGTTACAGCC 1646 TCTGGAGAGACCCTT 1647 CCAGGCTCAGTCTG 1648 AACCGTTACAGCCCAGAATCCCAGGCTCAGTCTGTCC
TCCATC
NCOR2 NM_006312 1649 CGTCATCTACGAA 1650 GAGCACTGGGTCACA 1651 CCTCATAGGACAAG 1652 CGTCATCTACGAAGGCAAGAAGGGCCACGTCTTGTC
ACGTGG
NDRG1 NM_006096 1653 AGGGCAACATTCC 1654 CAGTGCTCCTACTCC 1655 CTGCAAGGACACTC 1656 AGGGCAACATTCCACAGCTGCCCTGGCTGTGATGAG
ATCACA
NDUFS5 NM_004552 1657 AGAAGAGTCAAGG 1658 AGGCCGAACCTTTTC 1659 TGTCCAAGAAAGGC 1660 AGAAGAGTCAAGGGCACGAGCATCGGGTAGCCATGC
ATGGCT
NEK2 NM_002497 1661 GTGAGGCAGCGCGAC 1662 TGCCAATGGTGTACAA 1663 TGCCTTCCCGGGCT 1664 GTGAGGCAGCGCGACTCTGGCGACTGGCCGGCCATGCCT
TCT CACTTCA GAGGACT TCCCGGGCTGAGGACTATGAAGTGTTGTACACC
NETO2 NM_018092 1665 CCAGGGCACCATA 1666 AACGGTAAATCAAGG 1667 AGCCAACCCTTTTC 1668 CCAGGGCACCATACTGTTTCCAGCAGCCAACCCTTTT
TCCCAT
NEXN NM_144573 1669 AGGAGGAGGAAGA 1670 GAGCTCCTGATCTGG 1671 TCATCTTCAGCAGT 1672 AGGAGGAGGAAGAAGGTAGCATCATGAATGGCTCCA
GGAGCC
NFAT5 NM_006599 1673 CTGAACCCCTCTC 1674 AGGAAACGATGGCGA 1675 CGAGAATCAGTCCC 1676 CTGAACCCCTCTCCTGGTCACCGAGAATCAGTCCCCG
CGTGGA
NFATC2 NM_173091 1677 CAGTCAAGGTCAG 1678 CTTTGGCTCGTGGCAT 1679 CGGGTTCCTACCCC 1680 CAGTCAAGGTCAGAGGCTGAGCCCGGGTTCCTACCC
ACAGTC
NFKB1 NM_003998 1681 CAGACCAAGGAGA 1682 AGCTGCCAGTGCTAT 1683 AAGCTGTAAACATG 1684 CAGACCAAGGAGATGGACCTCAGCGTGGTGCGGCTC
AGCCGC
NFKBIA NM_020529 1685 C TACTGGACGACC 1686 CCTTGACCATCTGCTC 1687 CTCGTCTTTCATGG 1688 CTACTGGACGACCGCCACGACAGCGGCCTGGACTCC
AGTCCA
NME1 NM_000269 1689 CCAACCCTGCAGACT 1690 ATGTATAATGTTCCTG 1691 CCTGGGACCATCCG 1692 CCAACCCTGCAGACTCCAAGCCTGGGACCATCCGTGGAG
CCAA CCAACTTGTATG TGGAGACTTCT ACTTCTGCATACAAGTTGGCAGGAACATTATAC
NNMT NM_006169 1693 CCTAGGGCAGGGA 1694 CTAGTCCAGCCAAAC 1695 CCCTCTCCTCATGC 1696 CCTAGGGCAGGGATGGAGAGAGAGTCTGGGCATGAG
CCAGAC
NOS3 NM_000603 1697 ATCTCCGCCTCGC 1698 TCGGAGCCATACAGG 1699 TTCACTCGCTTCGC 1700 ATCTCCGCCTCGCTCATGGGCACGGTGATGGCGAAG
CATCAC
NOX4 NM_016931 1701 CCTCAACTGCAGCCT 1702 TGCTTGGAACCTTCTG 1703 CCGAACACTCTTGG 1704 CCTCAACTGCAGCCTTATCCTTTTACCCATGTGCCGAAC
TATCC TGAT CTTACCTCCG ACTCTTGGCTTACCTCCGAGGATCACAGAAGGTTC
NPBWR1 NM_005285 1705 TCACCAACCTGTT 1706 GATGTTGATGGGCAG 1707 ATCGCCGACGAGCT 1708 TCACCAACCTGTTCATCCTCAACCTGGCCATCGCCGA
CTTCAC
NPM1 NM_002520 1709 AATGTTGTCCAGGTT 1710 CAAGCAAAGGGTGGAG 1711 AACAGGCATTTTGG 1712 AATGTTGTCCAGGTTCTATTGCCAAGAATGTGTTGTCCA
CTATTGC TTC ACAACACATTCTTG AAATGCCTGTTTAGTTTTTAAAGATGGAACTCCAC
NRG1 NM_013957 1713 CGAGACTCTCCTCAT
AGTGAAAGGTA 1714 CTTGGCGTGTGGAAAT 1715 ATGACCACCCCGGC 1716 CGAGACTCTCCTCATAGTGAAAGGTATGTGTCAGCCATG
CTACAG TCGTATGTCA ACCACCCCGGCTCGTATGTCACCTGTAGATTTCC
NRIP3 NM_020645 1717 CCCACAAGCATGA 1718 TGCTCAATCTGGCCC 1719 AGCTTTCTCTACCC 1720 CCCACAAGCATGAAGGAGAAAAGCTTTCTCTACCCC
CGGCAT
NRP1 NM_003873 1721 CAGCTCTCTCCACGC 1722 CCCAGCAGCTCCATTC 1723 CAGGATCTACCCCG 1724 CAGCTCTCTCCACGCGATTCATCAGGATCTACCCCGAGA
GATTC TGA AGAGAGCCACTCAT GAGCCACTCATGGCGGACTGGGGCTCAGAATGGA
NUP62 NM_153719 1725 AGCCTCTTTGCGTCA 1726 CTGTGGTCACAGGGGT 1727 TCATCTGCCACCAC 1728 AGCCTCTTTGCGTCAATAGCAACTGCTCCAACCTCATCT
ATAGC ACAG TGGACTCTCC GCCACCACTGGACTCTCCCTCTGTACCCCTGTGAC
OAZ1 NM_004152 1729 AGCAAGGACAGCT 1730 GAAGACATGGTCGGC 1731 CTGCTCCTCAGCGA 1732 AGCAAGGACAGCTTTGCAGTTCTCCTGGAGTTCGCTG
ACTCCA
OCLN NM_002538 1733 CCCTCCCATCCGA 1734 GACGCGGGAGTGTAG 1735 CTCCTCCCTCGGTG 1736 CCCTCCCATCCGAGTTTCAGGTGAATTGGTCACCGAG
ACCAAT
ODC1 NM_002539 1737 AGAGATCACCGGCGT 1738 CGGGCTCAGCTATGAT 1739 CCAGCGTTGGACAA 1740 AGAGATCACCGGCGTAATCAACCCAGCGTTGGACAAATA
AATCAA TCTCA ATACTTTCCGTCA CTTTCCGTCAGACTCTGGAGTGAGAATCATAGCT
OLFML2 NM_015441 1741 CATGTTGGAAGGA 1742 CACCAGTTTGGTGGT 1743 TGGCCTGGATCTCC 1744 CATGTTGGAAGGAGCGTTCTATGGCCTGGATCTCCTG
TGAAGC
OLFML3 NM_020190 1745 TCAGAACTGAGGC 1746 CCAGATAGTCTACCT 1747 CAGACGATCCACTC 1748 TCAGAACTGAGGCCGACACCATCTCCGGGAGAGTGG
TCCCGG
OMD NM_005014 1749 CGCAAACTCAAGACT 1750 CAGTCACAGCCTCAAT 1751 TCCGATGCACATTC 1752 CGCAAACTCAAGACTATCCCAAATATTCCGATGCACATT
ATCCCA TTCATT AGCAACTCTACC CAGCAACTCTACCTTCAGTTCAATGAAATTGAGG
OR51E1 NM_152430 1753 GCATGCTTTCAGG 1754 AGAAGATGGCCAGCA 1755 TCCTCATCTCCACC 1756 GCATGCTTTCAGGCATTGACATCCTCATCTCCACCTC
TCATCC
OR51E2 NM_030774 1757 TATGGTGCCAAAA 1758 GTCCTTGTCACAGCT 1759 ACATAGCCAGCACC 1760 TATGGTGCCAAAACCAAACAGATCAGAACACGGGTG
CGTGTT
OSM NM_020530 1761 GTTTCTGAAGGGG 1762 AGGTGTCTGGTTTGG 1763 CTGAGCTGGCCTCC 1764 GTTTCTGAAGGGGAGGTCACAGCCTGAGCTGGCCTC
TATGCC
PAGE1 NM_003785 1765 CAACCTGACGAAGTG 1766 CAGATGCTCCCTCATC 1767 CCAACTCAAAGTCA 1768 CAACCTGACGAAGTGGAATCACCAACTCAAAGTCAGGAT
GAATC CTCT GGATTCTACACCTG TCTACACCTGCTGAAGAGAGAGAGGATGAGGGA
C
PAGE4 NM_007003 1769 GAATCTCAGCAAGAG 1770 GTTCTTCGATCGGAGG 1771 CCAACTGACAATCA 1772 GAATCTCAGCAAGAGGAACCACCAACTGACAATCAGGAT
GAACCA TGTT GGATATTGAACCTG ATTGAACCTGGACAAGAGAGAGAAGGAACACCT
G
PAK6 NM_020168 1773 CCTCCAGGTCACC 1774 GTCCCTTCAGGCCAG 1775 AGTTTCAGGAAGGC 1776 CCTCCAGGTCACCCACAGCCAGTTTCAGGAAGGCTG
TGCCCC
PATE1 NM_138294 1777 TGGTAATCCCTGG 1778 TCCACCTTATGCCTTT 1779 CAGCACAGTTCTTT 1780 TGGTAATCCCTGGTTAACCTTCATGGGCTGCCTAAAG
AGGCAG
PAC3 NM_015342 1781 CGTGATTGTCAGG 1782 AGAAAGGGGAGATGC 1783 CTGAGATGCTCCCT 1784 CGTGATTGTCAGGAGCAAGACCTGAGATGCTCCCTG
GCCTTC
PCDHGB NM_018927 1785 CCCAGCGTTGAAG 1786 GAAACGCCAGTCCGT 1787 ATTCTTAAACAGCA 1788 CCCAGCGTTGAAGCAGATAAGAAGATTCTTAAACAG
AGCCCC
PCNA NM_002592 1789 GAAGGTGTTGGAG 1790 GGTTTACACCGCTGG 1791 ATCCCAGCAGGCCT 1792 GAAGGTGTTGGAGGCACTCAAGGACCTCATCAACGA
CGTTGA
PDE9A NM_001001570 1793 TTCCACAACTTCCGG 1794 AGACTGCAGAGCCAGA 1795 TACATCATCTGGGC 1796 TTCCACAACTTCCGGCACTGCTTCTGCGTGGCCCAGATG
CAC CCA CACGCAGAAG ATGTACAGCATGGTCTGGCTCTGCAGTCT
PDGFRB NM_002609 1797 CCAGCTCTCCTTCC 1798 GGGTGGCTCTCACTT 1799 ATCAATGTCCCTGT 1800 CCAGCTCTCCTTCCAGCTACAGATCAATGTCCCTGTC
CCGAGT
PECAM1 NM_000442 1801 TGTATTTCAAGACCT 1802 TTAGCCTGAGGAATTG 1803 TTTATGAACCTGCC 1804 TGTATTTCAAGACCTCTGTGCACTTATTTATGAACCTGC
CTGTGCACTT CTGTGTT CTGCTCCCACA CCTGCTCCCACAGAACACAGCAATTCCTCAGGCT
PEX10 NM_153818 1805 GGAGAAGTTCCCTCC 1806 ATCTGTGTCCAGGCCC 1807 CTACCTTCGGCACT 1808 GGAGAAGTTCCCTCCCCAGAAGCTCATCTACCTTCGGCA
CCAG AC ACCGCTGAGC CTACCGCTGAGCCGGCGCCCGGGTGGGCCTGGAC
PGD NM_002631 1809 ATTCCCATGCCCT 1810 CTGGCTGGAAGCATC 1811 ACTGCCCTCTCCTT 1812 ATTCCCATGCCCTGTTTTACCACTGCCCTCTCCTTCT
CTATGA
PGF NM_002632 1813 GTGGTTTTCCCTCG 1814 AGCAAGGGAACAGCC 1815 ATCTTCTCAGACGT 1816 GTGGTTTTCCCTCGGAGCCCCCTGGCTCGGGACGTCT
CCCGAG
PGK1 NM_000291 1817 AGAGCCAGTTGCTGT 1818 CTGGGCCTACACAGTC 1819 TCTCTGCTGGGCAA 1820 AGAGCCAGTTGCTGTAGAACTCAAATCTCTGCTGGGCAA
AGAACTCAA CTTCA GGATGTTCTGTTC GGATGTTCTGTTCTTGAAGGACTGTGTAGGCCCA
PGR NM_000926 1821 GATAAAGGAGCCG 1822 TCACAAGTCCGGCAC 1823 TAAATTGCCGTCGC 1824 GATAAAGGAGCCGCGTGTCACTAAATTGCCGTCGCA
AGCCGC
PHTF2 NM_020432 1825 GATATGGCTGATG 1826 GGTTTGGGTGTTCTTG 1827 ACAATCTGGCAATG 1828 GATATGGCTGATGCTGCTCCTGGGAACTGTGCATTGC
CACAGT
PIK3C2A NM_002645 1829 ATACCAATCACCGCA 1830 CACACTAGCATTTCTC 1831 TGTGCTGTGACTGG 1832 ATACCAATCACCGCACAAACCCAGGCTATTTGTTAAGTC
CAAACC CGCATA ACTTAACAAATAGC CAGTCACAGCACAAAGAAACATATGCGGAGAAAA
CT
PIK3CA NM_006218 1833 GTGATTGAAGAGC 1834 GTCCTGCGTGGGAAT 1835 TCCTGCTTCTCGGG 1836 GTGATTGAAGAGCATGCCAATTGGTCTGTATCCCGA
ATACAG
PIK3CG NM_002649 1837 GGAGAACTCAATG 1838 TGATGCTTAGGCAGG 1839 TTCTGGACAATTAC 1840 GGAGAACTCAATGTCCATCTCCATTCTTCTGGACAAT
TGCCAC
PIM1 NM_002648 1841 CTGCTCAAGGACA 1842 GGATCCACTCTGGAG 1843 TACACTCGGGTCCC 1844 CTGCTCAAGGACACCGTCTACACGGACTTCGATGGG
ATCGAA
PLA2G7 NM_005084 1845 CCTGGCTGTGGTT 1846 TGACCCATGCTGATG 1847 TGGCAATACATAAA 1848 CCTGGCTGTGGTTTATCCTTTTGACTGGCAATACATA
TCCTGT
PLAU NM_002658 1849 GTGGATGTGCCCT 1850 CTGCGGATCCAGGGT 1851 AAGCCAGGCGTCTA 1852 GTGGATGTGCCCTGAAGGACAAGCCAGGCGTCTACA
CACGAG
PLAUR NM_002659 1853 CCCATGGATGCTC 1854 CCGGTGGCTACCAGA 1855 CATTGACTGCCGAG 1856 CCCATGGATGCTCCTCTGAAGAGACTTTCCTCATTGA
GCCCCA
PLG NM_000301 1857 GGCAAAATTTCCA 1858 ATGTATCCATGAGCG 1859 TGCCAGGCCTGGGA 1860 GGCAAAATTTCCAAGACCATGTCTGGACTGGAATGC
CTCTCA
PLK1 NM_005030 1861 AATGAATACAGTATT 1862 TGTCTGAAGCATCTTC 1863 AACCCCGTGGCCGC 1864 AATGAATACAGTATTCCCAAGCACATCAACCCCGTGGCC
CCCAAGCACAT TGGATGA CTCC GCCTCCCTCATCCAGAAGATGCTTCAGACA
PLOD2 NM_000935 1865 CAGGGAGGTGGTTGC 1866 TCTCCCAGGATGCATG 1867 TCCAGCCTTTTCGT 1868 CAGGGAGGTGGTTGCAAATTTCTAAGGTACAATTGCTCT
AAAT AAG GGTGACTCAA ATTGAGTCACCACGAAAAGGCTGGAGCTTCATG
PLP2 NM_002668 1869 CCTGATCTGCTTCA 1870 GCAGCAAGGATCATC 1871 ACACCAGGCTACTC 1872 CCTGATCTGCTTCAGTGCCTCCACACCAGGCTACTCC
CTCCCT
PNLIPRP NM_005396 1873 TGGAGAAGGTGAA 1874 CACGGCTTGGGTGTA 1875 ACCCGTGCCTCCAG 1876 TGGAGAAGGTGAACTGCATCTGTGTGGACTGGAGGC
TCCACA
POSTN NM_006475 1877 GTGGCCCAATTAG 1878 TCACAGGTGCCAGCA 1879 TTCTCCATCTGGCC 1880 GTGGCCCAATTAGGCTTGGCATCTGCTCTGAGGCCA
TCAGAG
PPAP2B NM_003713 1881 ACAAGCACCATCC 1882 CACGAAGAAAACTAT 1883 ACCAGGGCTCCTTG 1884 ACAAGCACCATCCCAGTGATGTTCTGGCAGGATTTGC
AGCAAA
PPFIA3 NM_003660 1885 CCTGGAGCTCCGT 1886 AGCCACATAGGGATC 1887 CACCCACTTTACCT 1888 CCTGGAGCTCCGTTACTCTCAGGCACCCACTTTACCT
TCTGGT
PP1R12A NM_002480 1889 CGGCAAGGGGTTGAT 1890 TGCCTGGCATCTCTAA 1891 CCGTTCTTCTTCCT 1892 CGGCAAGGGGTTGATATAGAAGCAGCTCGAAAGGAAGAA
ATAGA GCA TTCGAGCTGC GAACGGATCATGCTTAGAGATGCCAGGCA
PPP3CA NM_000944 1893 ATACTCCGAGCCC 1894 GGAAGCCTGTTGTTT 1895 TACATGCGGTACCC 1896 ATACTCCGAGCCCACGAAGCCCAAGATGCAGGGTAC
TGCATC
PRIMA1 NM_178013 1897 ATCCTCTTCCCTGA 1898 CCCAGCTGAGAGGGA 1899 TGACGCATCCAGGG 1900 ATCCTCTTCCCTGAGCCGCTGACGCATCCAGGGCTCT
CTCTAG
PRKAR1 NM_002735 1901 ACAAAACCATGAC 1902 TGTCATCCAGGTGAG 1903 AAGGCCATCTCCAA 1904 ACAAAACCATGACTGCGCTGGCCAAGGCCATCTCCA
GAACGT
PRKAR2B NM_002736 1905 TGATAATCGTGGGAG 1906 GCACCAGGAGAGGTAG 1907 CGAACTGGCCTTAA 1908 TGATAATCGTGGGAGTTTCGGCGAACTGGCCTTAATGTA
TTTCG CAGT TGTACAATACACCC CAATACACCCAGAGCAGCTACAATCACTGCTAC
A
PRKCA NM_002737 1909 CAAGCAATGCGTC 1910 GTAAATCCGCCCCCT 1911 CAGCCTCTGCGGAA 1912 CAAGCAATGCGTCATCAATGTCCCCAGCCTCTGCGG
TGGATC
PRKCB NM_002738 1913 GACCCAGCTCCAC 1914 CCCATTCACGTACTCC 1915 CCAGACCATGGGAC 1916 GACCCAGCTCCACTCCTGCTTCCAGACCATGGACCGC
CGCCTGT
PROM1 NM_006017 1917 CTATGACAGGCAT 1918 CTCCAACCATGAGGA 1919 ACCCGAGGCTGTGT 1920 CTATGACAGGCATGCCACCCCGACCACCCGAGGCTG
CTCCAA
PROS1 NM_000313 1921 GCAGCACAGGAAT 1922 CCCACCTATCCAACCT 1923 CTCATCCTGACAGA 1924 GCAGCACAGGAATCTTCTTCTTGGCAGCTGCAGTCTG
CTGCAG
PSCA NM_005672 1925 ACCGTCATCAGCAAA 1926 CGTGATGTTCTTCTTG 1927 CCTGTGAGTCATCC 1928 ACCGTCATCAGCAAAGGCTGCAGCTTGAACTGCGTGGAT
GGCT CCC ACGCAGTTCA GACTCACAGGACTACTACGTGGGCAAGAAGAAC
PSMD13 NM_002817 1929 GGAGGAGCTCTACAC 1930 CGGATCCTGCACAAAA 1931 CCTGAAGTGTCAGC 1932 GGAGGAGCTCTACACGAAGAAGTTGTGGCATCAGCTGAC
GAAGAAG TCA TGATGCCACA ACTTCAGGTGCTTGATTTTGTGCAGGATCCG
PTCH1 NM_000264 1933 CCACGACAAAGCC 1934 TACTCGATGGGCTCT 1935 CCTGAAACAAGGCT 1936 CCACGACAAAGCCGACTACATGCCTGAAACAAGGCT
GAGAAT
PTEN NM_000314 1937 TGGCTAAGTGAAGAT 1938 TGCACATATCATTAC 1939 CCTTTCCAGCTTTA 1940 TGGCTAAGTGAAGATGACAATCATGTTGCAGCAATTCAC
GACAATCATG ACCAGTTCGT CAGTGAATTGCTGC TGTAAAGCTGGAAAGGGACGAACTGGTGTAATG
A
PTGER3 NM_000957 1941 TAACTGGGGCAAC 1942 TTGCAGGAAAAGGTG 1943 CCTTTGCCTTCCTG 1944 TAACTGGGGCAACTTTTCTTCGCCTCTGCCTTTGCC
GGGCTC
PTGS2 NM_000963 1945 GAATCATTCACCAGG 1946 CTGTACTGCGGGTGGA 1947 CCTACCACCAGCAA 1948 GAATCATTCACCAGGCAAATTGCTGGCAGGGTTGCTGGT
CAAATTG ACAT CCCTGCCA GGTAGGAATGTTCCACCCGCAGTACAG
PTH1R NM_000316 1949 CGAGGTACAAGCTGA 1950 GCGTGCCTTTCGCTTG 1951 CCAGTGCCAGTGTC 1952 CGAGGTACAAGCTGAGATCAAGAAATCTTGGAGCCGCTG
GATCAAGAA AA CAGCGGCT GACACTGGCACTGGACTTCAAGCGAAAGGCACG
PTHLH NM_002820 1953 AGTGACTGGGAGTGG 1954 AAGCCTGTTACCGTGA 1955 TGACACCTCCACAA 1956 AGTGACTGGGAGTGGGCTAGAAGGGGACCACCTGTCTGA
GCTAGAA ATCGA CGTCGCTGGA CACCTCCACAACGTCGCTGGAGCTCGATTCACG
PTK2 NM_005607 1957 GACCGGTCGAATG 1958 CTGGACATCTCGATG 1959 ACCAGGCCCGTCAC 1960 GACCGGTCGAATGATAAGGTGTACGAGAATGTGACG
ATTCTC
PTK2B NM_004103 1961 CAAGCCCAGCCGA 1962 GAACCTGGAACTGCA 1963 CTCCGCAAACCAAC 1964 CAAGCCCAGCCGACCTAAGTACAGACCCCCTCCGCA
CTCCTG
PTK6 NM_005975 1965 GTGCAGGAAAGGTTC 1966 GCACACACGATGGAGT 1967 AGTGTCTGCGTCCA 1968 GTGCAGGAAAGGTTCACAAATGTGGAGTGTCTGCGTCCA
ACAAA AAGG ATACACGCGT ATACACGCGTGTGCTCCTCTCCTTACTCCATCGT
PTK7 NM_002821 1969 TCAGAGGACTCAC 1970 CATACACCTCCACGC 1971 CGCAAGGTCCCATT 1972 TCAGAGGACTCACGGTTCGAGGTCTTCAAGAATGGG
CTTGAA
PTPN1 NM_002827 1973 AATGAGGAAGTTT 1974 CTTCGATCACAGCCA 1975 CTGATCCAGACAGC 1976 AATGAGGAAGTTTCGGATGGGGCTGATCCAGACAGC
CGACCA
PTPRK NM_002844 1977 TCAAACCCTCCCA 1978 AGCAGCCAGTTCGTC 1979 CCCCATCGTTGTAC 1980 TCAAACCCTCCCAGTGCTGGCCCCATCGTTGTACATT
ATTGCA
PTTG1 NM_004219 1981 GGCTACTCTGATCTA 1982 GCTTCAGCCCATCCTT 1983 CACACGGGTGCCTG 1984 GGCTACTCTGATCTATGTTGATAAGGAAAATGGAGAACC
TGTTGATAAGG AGCA GTTCTCCA AGGCACCCGTGTGGTTGCTAAGGATGGGCTGAA
PYCARD NM_013258 1985 CTTTATAGACCAG 1986 AGCATCCAGCAGCCA 1987 ACGTTTGTGACCCT 1988 CTTTATAGACCAGCACCGGGCTGCGCTTATCGGCGAG
CGCGAT
RAB27A NM_004580 1989 TGAGAGATTAATG 1990 CCGGATGCTTTATTCG 1991 ACAAATTGCTTCTC 1992 TGAGAGATTAATGGGCATTGTGTACAAATTGCTTCTC
ACCATC
RAB30 NM_014488 1993 TAAAGGCTGAGGC 1994 CTCCCCAGCATCTCAT 1995 CCATCAGGGCAGTT 1996 TAAAGGCTGAGGCACGGAGAAGAAAAGGAATCAGCA
GCTGAT
RAB31 NM_006868 1997 CTGAAGGACCCTA 1998 ATGCAAAGCCAGTGT 1999 CTTCTCAAAGTGAG 2000 CTGAAGGACCCTACGCTCGGTGGCCTGGCACCTCAC
GTGCCA
RAD21 NM_006265 2001 TAGGGATGGTATCTG 2002 TCGCGTACACCTCTGC 2003 CACTTAAAACGAAT 2004 TAGGGATGGTATCTGAAACAACAATGGTCACCCTCTTGA
AAACAACA TC CTCAAGAGGGTGAC GATTCGTTTTAAGTGTAATTCCATAATGAGCAGAG
CA
RAD51 NM_002875 2005 AGACTACTCGGGT 2006 AGCATCCGCAGAAAC 2007 CTTTCAGCCAGGCA 2008 AGACTACTCGGGTCGAGGTGAGCTTTCAGCCAGGCA
GATGCA
RAD9A NM_004584 2009 GCCATCTTCACCA 2010 CGGTGTCTGAGAGTG 2011 CTTTGCTGGACGGC 2012 GCCATCTTCACCATCAAGGACTCTTTGCTGGACGGCC
CACTTT
RAF1 NM_002880 2013 CGTCGTATGCGAG 2014 TGAAGGCGTGAGGTG 2015 TCCAGGATGCCTGT 2016 CGTCGTATGCGAGAGTCTGTTTCCAGGATGCCTGTTA
TAGTTC
RAGE NM_014226 2017 ATTAGGGGGACTTT 2018 GGGTGGAGATGTATT 2019 CCGGAGTGTCTATT 2020 ATTAGGGGACTTTGGCTCCTGCCGGAGTGTCTATTCC
CCAAGC
RALA NM_005402 2021 TGGTCCTGAATGT 2022 CCCCATTTCACCTCTT 2023 TTGTGTTTCTTGGG 2024 TGGTCCTGAATGTAGCGTGTAAGCTTGTGTTTCTTGG
CAGTCT
RALBP1 NM_006788 2025 GGTGTCAGATATAAA 2026 TTCGATATTGCCAGCA 2027 TGCTGTCCTGTCGG 2028 GGTGTCAGATATAAATGTGCAAATGCCTTCTTGCTGTCC
TGTGCAAATGC GCTATAAA TCTCAGTACGTTCA TGTCGGTCTCAGTACGTTCACTTTATAGCTGCTGG
RAP1B NM_001010942 2029 TGACAGCGTGAGAGG 2030 CTGAGCCAAGAACGAC 2031 CACGCATGATGCAA 2032 TGACAGCGTGAGAGGTACTAGGTTTTGACAAGCTTGCAT
TACTAGG TAGCTT GCTTGTCAAA CATGCGTGAGTATAAGCTAGTCGTTCTTGGCTCA
RARB NM_000965 2033 ATGAACCCTTGACCC 2034 GAGCTGGGTGAGATGC 2035 TGTGCTCTGCTGTG 2036 ATGAACCCTTGACCCCAAGTTCAAGTGGGAACACAGCAG
CAAGT TAGG TTCCCACTTG AGCACAGTCCTAGCATCTCACCCAGCTC
RASSF1 NM_007182 2037 AGGGCACGTGAAGTC 2038 AAAGAGTGCAAACTTG 2039 CACCACCAAGAACT 2040 AGGGCACGTGAAGTCATTGAGGCCCTGCTGCGAAAGTTC
ATTG CGG TTCGCAGCAG TTGGTGGTGGATGACCCCCGCAAGTTTGCACTCT
RB1 NM_000321 2041 CGAAGCCCTTACA 2042 GGACTCTTCAGGGGT 2043 CCCTTACGGATTCC 2044 CGAAGCCCTTACAAGTTTCCTAGTTCACCCTTACGGA
TGGAGG
RECK NM_021111 2045 GTCGCCGAGTGTG 2046 GTGGGATGATGGGTT 2047 TCAAGTGTCCTTCG 2048 GTCGCCGAGTGTGCTTCTGTCAAGTGTCCTTCGCTCT
CTCTTG
REG4 NM_032044 2049 TGCTAACTCCTGCAC 2050 TGCTAGGTTTCCCCTC 2051 TCCTCTTCCTTTCT 2052 TGCTAACTCCTGCACAGCCCCGTCCTCTTCCTTTCTGCT
AGCC TGAA GCTAGCCTGGC AGCCTGGCTAAATCTGCTCATTATTTCAGAGGGGA
RELA NM_021975 2053 CTGCCGGGATGGC 2054 CCAGGTTCTGGAAAC 2055 CTGAGCTCTGCCCG 2056 CTGCCGGGATGGCTTCTATGAGGCTGAGCTCTGCCC
GACCGC
RFX1 NM_002918 2057 TCCTCTCCAAGTTC 2058 CAGGCCCTGGTACAG 2059 TCCAATGGACCAAG 2060 TCCTCTCCAAGTTCGAGCCCGTGCTCCAATGGACCAA
CACTGT
RGS10 NM_001005339 2061 AGACATCCACGACAG 2062 CCATTTGGCTGTGCTC 2063 AGTTCCAGCAGCAG 2064 AGACATCCACGACAGCGATGGCAGTTCCAGCAGCAGCCA
CGAT TTG CCACCAGAG CCAGAGCCTCAAGAGCACAGCCAAATGG
RGS7 NM_002924 2065 CAGGCTGCAGAGAGC 2066 TTTGCTTGTGCTTCTG 2067 TGAAAATGAACTCC 2068 CAGGCTGCAGAGAGCATTTGCCCGGAAGTGGGAGTTCAT
ATTT CTTG CACTTCCGGG TTTCATGCAAGCAGAAGCACAAGCAAA
RHOA NM_001664 2069 TGGCATAGCTCTG 2070 TGCCACAGCTGCATG 2071 AAATGGGCTCAACC 2072 TGGCATAGCTCTGGGGTGGGCAGTTTTTTGAAAATG
AGAAA
RHOB NM_004040 2073 AAGCATGAACAGG 2074 CCTCCCCAAGTCAGT 2075 CTTTCCAACCCCTG 2076 AAGCATGAACAGGACTTGACCATCTTTCCAACCCCTG
GGGAAG
RHOC NM_175744 2077 CCCGTTCGGTCTG 2078 GAGCACTCAAGGTAG 2079 TCCGGTTCGCCATG 2080 CCCGTTCGGTCTGAGGAAGGCCGGGACATGGCGAAC
TCCCG
RLN1 NM_006911 2081 AGCTGAAGGCAGCCC 2082 TTGGAATCCTTTAATG 2083 TGAGAGGCAACCAT 2084 AGCTGAAGGCAGCCCTATCTGAGAGGCAACCATCATTAC
TATC CAGGT CATTACCAGAGC CAGAGCTACAGCAGTATGTACCTGCATTAAAGG
RND3 NM_005168 2085 TCGGAATTGGACT 2086 CTGGTTACTCCCCTCC 2087 TTTTAAGCCTGACT 2088 TCGGAATTGGACTTGGGAGGCGCGGTGAGGAGTCAG
CCTCAC
RNF114 NM_018683 2089 TGACAGGGGAAGT 2090 GGAAGACAGCTTTGG 2091 CCAGGTCAGCCCTT 2092 TGACAGGGGAAGTGGGTCCCCAGGTCAGCCCCTTCTC
CTCTTC
ROBO2 NM_002942 2093 CTACAAGGCCCAG 2094 CACCAGTGGCTTTAC 2095 CTGTACCATCCACT 2096 CTACAAGGCCCAGCCAACCAAACGCTGGCAGTGGAT
GCCAGC
RRM1 NM_001033 2097 GGGCTACTGGCAG 2098 CTCTCAGCATCGGTA 2099 CATTGGAATTGCCA 2100 GGGCTACTGGCAGCTACATTGCTGGGACTAATGGCA
TTAGTC
RRM2 NM_001034 2101 CAGCGGGATTAAA 2102 ATCTGCGTTGAAGCA 2103 CCAGCACAGCCAGT 2104 CAGCGGGATTAAACAGTCCTTTAACCAGCACAGCCA
TAAAAG
S100P NM_005980 2105 AGACAAGGATGCC 2106 GAAGTCCACCTGGGC 2107 TTGCTCAAGGACCT 2108 AGACAAGGATGCCGTGGATAAATTGCTCAAGGACCT
GGACGC
SAT1 NM_002970 2109 CCTTTTACCACTGC 2110 ACAATGCTGTGTCCTT 2111 TCCAGTGCTCTTTC 2112 CCTTTTACCACTGCCTGGTTGCGAAGTGCCGAAAGA
GGCACT
SCUBE2 NM_020974 2113 TGACAATCAGCACAC 2114 TGTGACTACAGCCGTG 2115 CAGGCCCTCTTCCG 2116 TGACAATCAGCACACCTGCATTCACCGCTCGGAAGAGGG
CTGCAT ATCCTTA AGCGGT CCTGAGCTGCATGAATAAGGATCACGGCTGTAG
SDC1 NM_002997 2117 GAAATTGACGAGG 2118 AGGAGCTAACGGAGA 2119 CTCTGAGCGCCTCC 2120 GAAATTGACGAGGGGTGTCTTGGGCAGAGCTGGCTC
ATCCAA
SDC2 NM_002998 2121 GGATTGAAGTGGC 2122 ACCAGCCACAGTACC 2123 AACTCCATCTCCTT 2124 GGATTGAAGTGGCTGGAAAGAGTGATGCCTGGGGAA
CCCCAG
SDHC NM_003001 2125 CTTCCCTCGGGTCT 2126 TTCCCTCCTGGTAAA 2127 TTACATCCTCCCTC 2128 CTTCCCTCGGGTCTCAGGCATTTACATCCTCCCTCTC
TCCCCG
SEC14L1 NM_001039573 2129 AGGGTTCCCATGTGA 2130 GCAGGCATGCTGTGGA 2131 CGGGCTTCTACATC 2132 AGGGTTCCCATGTGACCAGGTGGCCGGGCTTCTACATCC
CCAG AT CTGCAGTGG TGCAGTGGAAATTCCACAGCATGCCTGC
SEC23A NM_006364 2133 CGTGTGCATTAGA 2134 CCCATTACCATGTATC 2135 TCCTGGAGATGAAA 2136 CGTGTGCATTAGATCAGACAGGTCTCCTGGAGATGA
TGCTGT
SEMA3A NM_006080 2137 TTGGAATGCAGTC 2138 CTCTTCATTTCGCCTC 2139 TTGCCAATAGACCA 2140 TTGGAATGCAGTCCGAAGTCGCAGAGAGCGCTGGTC
GCGCTC
SEPT9 NM_006640 2141 CAGTGACCACGAG 2142 CTTCGATGGTACCCC 2143 TTGCCAATAGACCA 2144 CAGTGACCACGAGTACCAGGTCAACGGCAAGAGGAT
GCGCTC
SERPINA3 NM_001085 2145 GTGTGGCCCTGTCTG 2146 CCCTGTGCATGTGAGA 2147 AGGGAATCGCTGTC 2148 GTGTGGCCCTGTCTGCTTATCCTTGGAAGGTGACAGCGA
CTTA GCTAC ACCTTCCAAG TTCCCTGTGTAGCTCTCACATGCACAGGG
SERPINB5 NM_002639 2149 CAGATGGCCACTTTG 2150 GGCAGCATTAACCACA 2151 AGCTGACAACAGTG 2152 CAGATGGCCACTTTGAGAACATTTTAGCTGACAACAGTG
AGAACATT AGGATT TGAACGACCAGACC TGAACGACCAGACCAAAATCCTTGTGGTTAATG
SESN3 NM_144665 2153 GACCCTGGTTTTG 2154 GAGCTCGGAATGTTG 2155 TGCTCTTCTCCTCG 2156 GACCCTGGTTTTGGGTATGAAGACTTTGCCAGACGA
TCTGGC
SFRP4 NM_003014 2157 TACAGGATGAGGC 2158 GTTGTTAGGGCAAGG 2159 CCTGGGACAGCCTA 2160 TACAGGATGAGGCTGGGCATTGCCTGGGACAGCCTA
TGTAAG
SH3RF2 NM_152550 2161 CCATCACAACAGCCT 2162 CACTGGGGTGCTGATC 2163 AACCGGATGGTCCA 2164 CCATACAACAGCCTTGAACACTCTCAACCGGATGGTCCA
TGAAC TCTA TTCTCCTTCA TTCTCCTTCAGGGCGCCATATGGTAGAGATCAG
SH3YL1 NM_015677 2165 CCTCCAAAGCCAT 2166 CTTTGAGAGCCAGAG 2167 CACAGCAGTCATCT 2168 CCTCCAAAGCCATTGTCAAGACCACAGCAGTCATCT
GCACCA
SHH NM_000193 2169 GTCCAAGGCACAT 2170 GAAGCAGCCTCCCGA 2171 CACCGAGTTCTCTG 2172 GTCCAAGGCACATATCCACTGCTCGGTGAAAGCAGA
CTTTCA
SHMT2 NM_005412 2173 AGCGGGTGCTAGA 2174 ATGGCACTTCGGTCT 2175 CCATCACTGCCAAC 2176 AGCGGGTGCTAGAGCTTGTATCCATCACTGCCAACA
AAGAAC
SIM2 NM_005069 2177 GATGGTAGGAAGG 2178 CACAAGGAGCTGTGA 2179 CGCCTCTCCACGCA 2180 GATGGTAGGAAGGGATGTGCCCGCCTCTCCACGCAC
CTCAGC
SIPA1L1 NM_015556 2181 CTAGGACAGCTTG 2182 CATAACCGTAGGGCT 2183 CGCCACAATGCCCT 2184 CTAGGACAGCTTGGCTTCCATGTCAACTATGAGGGC
CATAGT
SKIL NM_005414 2185 AGAGGCTGAATAT 2186 CTATCGGCCTCAGCA 2187 CCAATCTCTGCCTC 2188 AGAGGCTGAATATGCAGGACAGTTGGCAGAACTGAG
AGTTCT
SLC22A3 NM_021977 2189 ATCGTCAGCGAGT 2190 CAGGATGGCTTGGGT 2191 CAGCATCCACGCAT 2192 ATCGTCAGCGAGTTTGACCTTGTCTGTGTCAATGCGT
TGACAC
SLC25A21 NM_030631 2193 AAGTGTTTTTCCCCC 2194 GGCCGATCGATAGTCT 2195 TCATGGTGCTGCAT 2196 AAGTGTTTTTCCCCCTTGAGATAATGGATATTTGCTATG
TTGAGAT CTCTT AGCAAATATCCA CAGCACCATGAAGAAGAGAGACTATCGATCGGCC
SLC44A1 NM_080546 2197 AGGACCGTAGCTG 2198 ATCCCATCCCAATGC 2199 TACCATGGCTGCTG 2200 AGGACCGTAGCTGCACAGACATACCATGGCTGCTGC
CTCTTC
SMAD4 NM_005359 2201 GGACATTACTGGC 2202 ACCAATACTCAGGAG 2203 TGCATTCCAGCCTC 2204 GGACATTACTGGCCTGTTCACAATGAGCTTGCATTCC
CCATTT
SMARCC2 NM_003075 2205 TACCGACTGAACCCC 2206 GACATCACCCGCTAGG 2207 TATCTTACCTCTAC 2208 TACCGACTGAACCCCCAAGAAGTATCTTACCTCTACCGC
CAA TTTC CGCCTGCCGC CTGCCGCCGAAACCTAGCGGGTGATGTC
SMARCD1 NM_003076 2209 CCGAGTTAGCATATC 2210 CCTTTGTGCCCAGCTG 2211 CCCACCCTTGCTGT 2212 CCGAGTTAGACATATCCCAGGCTCGCAGACTCAACACAG
CCAGG TC GTTGAGTCTG CAAGGGTGGGAGACAGCTGGGCACAAAGG
SMO NM_005631 2213 GGCATCCAGTGCC 2214 CGCGATGTAGCTGTG 2215 CTTCACAGAGGCTG 2216 GGCATCCAGTGCCAGAACCCGCTCTTCACAGAGGCT
AGCACC
SNA11 NM_005985 2217 CCCAATCGGAAGC 2218 GTAGGGCTGCTGGAA 2219 TCTGGATTAGAGTC 2220 CCCAATCGGAAGCCTAACTACAGCGAGCTGCAGGAC
CTGCAG
SNRPB2 NM_003092 2221 CGTTTCCTGCTTTT 2222 AGGTAGAAGGCGCAC 2223 CCCACCTAAGGCCT 2224 CGTTTCCTGCTTTTGGTTCTTACAGTAGTCGGCGTAG
ACGCCG
SOD1 NM_000454 2225 TGAAGAGAGGCAT 2226 AATAGACACATCGGC 2227 TTTGTCAGCAGTCA 2228 TGAAGAGAGGCATGTTGGAGACTTGGGCAATGTGAC
CATTGC
SORBS1 NM_015385 2229 GCAGATGAGTGGA 2230 AGCGAGTGAAGAGGG 2231 ATTTCCATTGGCAT 2232 GCAGATGAGTGGAGGCTTTCTTCCAGTGCTGATGCC
CAGCAC
SOX4 NM_003107 2233 AGATGATCTCGGG 2234 GCGCCCTTCAGTAGG 2235 CGAGTCCAGCATCT 2236 AGATGATCTCGGGAGACTGGCTCGAGTCCAGCATCT
CCAACC
SPARC NM_003118 2237 TCTTCCCTGTACACT 2238 AGCTCGGTGTGGGAGA 2239 TGGACCAGCACCCC 2240 TCTTCCCTGTACACTGGCAGTTCGGCCAGCTGGACCAGC
GGCAGTTC GGTA ATTGACGG ACCCCATTGACGGGTACCTCTCCCACACCGAGCT
SPARCL NM_004684 2241 GGCACAGTGCAAG 2242 GATTGAGCTCTCTCG 2243 ACTTCATCCCAAGC 2244 GGCACAGTGCAAGTGATGACTACTTCATCCCAAGCC
CAGGCC
SPDEF NM_012391 2245 CCATCCGCCAGTATT 2246 GGGTGCACGAACTGGT 2247 ATCATCCGGAAGCC 2248 CCATCCGCCAGTATTACAAGAAGGGCATCATCCGGAAGC
ACAAG AGA AGACATCTCC CAGACATCTCCCAGCGCCTCGTCTACCAGTTCGT
SPINK1 NM_003122 2249 CTGCCATATGACC 2250 GTTGAAAACTGCACC 2251 ACCACGTCTCTTCA 2252 CTGCCATATGACCCTTCCAGTCCCAGGCTTCTGAAGA
GAAGCC
SPINT1 NM_003710 2253 ATTCCCAGCACAG 2254 AGATGGCTACCACCA 2255 CTGTCGCAGTGTTC 2256 ATTCCCAGCACAGGCTCTGTGGAGATGGCTGTCGCA
CTGGTC
SPP1 NM_001040058 2257 TCACACATGGAAAGC 2258 GTTCAGGTCCTGGGCA 2259 TGAATGGTGCATAC 2260 TCACACATGGAAAGCGAGGAGTTGAATGGTGCATACAAG
GAGG AC AAGGCCATCC GCCATCCCCGTTGCCCAGGACCTGAAC
SQLE NM_003219 2261 ATTTTCGAGGCCAAA 2262 CCTGAGCAAGGATATT 2263 TGGGCAAGAAAAAC 2264 ATTTTCGAGGCCAAAAAATCATTTACTGGGCAAGAAAAA
AAATC CACG ATCTCATTCCTTTG CATCTCATTCCTTTGTCGTGAATATCCTTGCTC
SRC NM_005417 2265 TGAGGAGTGGTATTT 2266 CTCTCGGGTTCTCTGC 2267 AACCGCTCTGACTC 2268 TGAGGAGTGGTATTTTGGCAAGATCACCAGACGGGAGTC
TGGCAAGA ATTGA CCGTCTGGTG AGAGCGGTTACTGCTCAATGCAGAGAACCCGAG
SRD5A1 NM_001047 2269 GGGCTGGAATCTG 2270 CCATGACTGCACAAT 2771 CCTCTCTCGGAGGC 2272 GGGCTGGAATCTGTCTAGGAGCCCTCTCTCGGAGGC
CACAGA
SRD5A2 NM_000348 2273 GTAGGTCTCCTGGCG 2274 TCCCTGGAAGGGTAGG 2275 AGACACCACTCAGA 2276 GTAGGTCTCCTGGCGTTCTGCCAGCTGGCCTGGGGATTC
TTCTG AGTAA ATCCCCAGGC TGAGTGGTGTCTGCTTAGAGTTTACTCCTACCCTT
ST5 NM_005418 2277 CCTGTCCTGCCAG 2278 CAGCTGCACAAAACT 2279 AGTCACGAGCACCC 2280 CCTGTCCTGCCAGAGCATGGATGAAGTTTCGCTGGGT
AGCGA
STAT1 NM_007315 2281 GGGCTCAGCTTTCAG 2282 ACATGTTCAGCTGGTC 2283 TGGCAGTTTTCTTC 2284 GGGCTCAGCTTTCAGAAGTGCTGAGTTGGCAGTTTTCTT
AAGTG CACA TGTCACCAAAA CTGTCACCAAAAGAGGTCTCAATGTGGACCAGCT
STAT3 NM_003150 2285 TCACATGCCACTTT 2286 CTTGCAGGAAGCGGC 2287 TCCTGGGAGAGATT 2288 TCACATGCCACTTTGGTGTTTCATAATCTCCTGGGAG
GACCAG
STAT5A NM_003152 2289 GAGGCGCTCAACATG 2290 GCCAGGAACACGAGGT 2291 CGGTTGCTCTGCAC 2292 GAGGCGCTCAACATGAAATTCAAGGCCGAAGTGCAGAGC
AAATTC TCTC TTCGGCCT AACCGGGGCCTGACCAAGGAGAACCTCGTGTTC
STAT5B NM_012448 2293 CCAGTGGTGGTGA 2294 GCAAAAGCATTGTCC 2295 CAGCCAGGACAACA 2296 CCAGTGGTGGTGATCGTTCATGGCAGCCAGGACAAC
ATGCG
STMN1 NM_005563 2297 AATACCCAACGCA 2298 GGAGACAATGCAAAC 2299 CACGTTCTCTGCCC 2300 AATACCCAACGCACAAATGACCGCACGTTCTCTGCC
CGTTTC
STS NM_000351 2301 GAAGATCCCTTTCCT 2302 GGATGATGTTCGGCCT 2303 CTGCGTGGCTCTCG 2304 GAAGATCCCTTTCCTCCTACTGTTCTTTCTGTGGGAAGC
CCTACTGTTC TGAT GCTTCCCA CGAGAGCCACGCAGCATCAAGGCCGAACATCATC
SULF1 NM_015170 2305 TGCAGTTGTAGGGAG 2306 TCTCAAGAATTGCCGT 2307 TACCGTGCCAGCAG 2308 TGCAGTTGTAGGGAGTCTGGTTACCGTGCCAGCAGAAGC
TCTGG TGAC AAGCCAAAG CAAAGAAAGAGTCAACGGCAATTCTTGAGA
SUMO1 NM_003352 2309 GTGAAGCCACCGT 2310 CCTTCCTTCTTATCCC 2311 CTGACCAGGAGGCA 2312 GTGAAGCCACCGTCATCATGTCTGACCAGGAGGCAA
AAACCT
SVIL NM_003174 2313 ACTTGCCCAGCAC 2314 GACACCATCCGTGTC 2315 ACCCCAGGACTGAT 2316 ACTTGCCCAGCACAAGGAAGACCCCAGGACTGATGT
GTCAAG
TAF2 NM_003184 2317 GCGCTCCACTCTCAG 2318 CTTGTGCTCATGGTGA 2319 AGCCTCCAAACACA 2320 GCGCTCCACTCTCAGTCTTTACTAAGGAATCTACAGCCT
TCTTT TGGT GTGACCACCA CCAAACACAGTGACCACCATCACCACCATCACCAT
TARP NM_001003799 2321 GAGCAACACGATTCT 2322 GGCACCGTTAACCAGC 2323 TCTTCATGGTGTTC 2324 GAGCAACACGATTCTGGGATCCCAGGAGGGGAACACCAT
GGGA TAAAT CCCTCCTGG GAAGACTAACGACACATACATGAAATTTAGCTG
TBP NM_003194 2325 GCCCGAAACGCCG 2326 CGTGGCTCTCTTATCC 2327 TACCGCAGCAAACC 2328 GCCCGAAACGCCGAATATAATCCCAAGCGGTTTGCT
GCTTGG
TFDP1 NM_007111 2329 TGCGAAGTGCTTTTG 2330 GCCTTCCAGACAGTCT 2331 CGCACCAGCATGGC 2332 TGCGAAGTGCTTTTGTTTGTTTGTTTTCGTTTGGTTAAA
TTTGT CCAT AATAAGCTTT GCTTATTGCCATGCTGGTGCGGCTATGGAGACTGTC
TFF1 NM_003225 2333 GCCCTCCCAGTGTGC 2334 CGTCGATGGTATTAGG 2335 TGCTGTTTCGACGA 2336 GCCCTCCCAGTGTGCAAATAAGGGCTGCTGTTTCGACGA
AAAT ATAGAAGCA CACCGTTCG CACCGTTCGTGGGGTCCCCTGGTGCTTCTATCCTA
TFF3 NM_003226 2337 AGGCACTGTTCATCT 2338 CATCAGGCTCCAGATA 2339 CAGAAGCGCTTGCC 2340 AGGCACTGTTCATCTCAGCTTTTCTGTCCCTTTGCTCCC
CAGTTTTTCT TGAACTTTC GGGAGCAAAGG GGCAAGCGCTTCTGCTGAAAGTTCATATCTGGAG
TGFA NM_003236 2341 GGTGTGCCACAGACC 2342 ACGGAGTTCTTGACAG 2343 TTGGCCTGTAATCA 2344 GGTGTGCCACAGACCTTCCTACTTGGCCTGTAATCACCT
TTCCT AGTTTTGA CCTGTGCAGCCTT GTGCAGCCTTTTGTGGGCCTTCAAAACTCTGTCAA
TGFB1II NM_001042454 2345 GCTACTTTGAGCGCT 2346 GGTCACCATCTTGTGT 2347 CAAGATGTGGCTTC 2348 GCTACTTTGAGCGCTTCTCGCCAAGATGTGGCTTCTGCA
TCTCG CGG TGCAACCAGC ACCAGCCCATCCGACACAAGATGGTGACC
TGFB2 NM_003238 2349 ACCAGTCCCCCAG 2350 CCTGGTGCTGTTGTA 2351 TCCTGAGCCCGAGG 2352 ACCAGTCCCCCAGAAGACTATCCTGAGCCCGAGGAA
AAGTCC
TGFB3 NM_003239 2353 GGATCGAGCTCTT 2354 GCCACCGATATAGCG 2355 CGGCCAGATGAGCA 2356 GGATCGAGCTCTTCCAGATCCTTCGGCCAGATGAGC
CATTGC
TGFBR2 NM_003242 2357 AACACCAATGGGT 2358 CCTCTTCATCAGGCC 2359 TTCTGGGCTCCTGA 2360 AACACCAATGGGTTCCATCTTTCTGGGCTCCTGATTG
TTGCTC
THBS2 NM_003247 2361 CAAGACTGGCTACAT 2362 CAGCGTAGGTTTGGTC 2363 TGAGTCTGCCATGA 2364 CAAGACTGGCTACATCAGAGTCTTAGTGCATGAAGGAAA
CAGAGTCTTAG ATAGATAGG CCTGTTTTCCTTCA ACAGGTCATGGCAGACTCAGGACCTATCTATGA
T
THY1 NM_006288 2365 GGACAAGACCCTC 2366 TTGGAGGCTGTGGGT 2367 CAAGCTCCCAAGAG 2368 GGACAAGACCCTCTCAGGCTGTCCCAAGCTCCCAAG
CTTCCA
TIAM1 NM_003253 2369 GTCCCTGGCTGAA 2370 GGGCTCCCGAAGTCT 2371 TGGAGCCCTTCTCC 2372 GTCCCTGGCTGAAAATGGCCTGGAGCCCTTCTCCCAA
CAAGAT
TIMP2 NM_003255 2373 TCACCCTCTGTGA 2374 TGTGGTTCAGGCTCTT 2375 CCCTGGGACACCCT 2376 TCACCCTCTGTGACTTCATCGTGCCCTGGGACACCCT
GAGCAC
TIMP3 NM_000362 2377 CTACCTGCCTTGCT 2378 ACCGAAATTGGAGAG 2379 CCAAGAACGAGTGT 2380 CTACCTGCCTTGCTTTGTGACTTCCAAGAACGAGTGT
CTCTGG
TK1 NM_003258 2381 GCCGGGAAGACCGTA 2382 CAGCGGCACCAGGTTC 2383 CAAATGGCTTCCTC 2384 GCCGGGAAGACCGTAATTGTGGCTGCACTGGATGGGACC
ATTGT AG TGGAAGGTCCCA TTCCAGAGGAAGCCATTTGGGGCCATCCTGAAC
TMPRSS NM_005656 2385 GGACAGTGTGCAC 2386 CTCCCACGAGGAAGG 2387 AAGCACTGTGCATC 2388 GGACAGTGTGCACCTCAAAGACTAAGAAAGCACTGT
ACCTTG
TMPRSS DQ204772 2389 GAGGCGGAGGGCGAG 2390 ACTGGTCCTCACTCAC 2391 TAAGGCTTCCTGCC 2392 GAGGCGGAGGCGGAGGGCGAGGGGCGGGGAGCGCCGCCT
2ERGA AACT GCGCTCCA GGAGCGCGGCAGGAAGCCTTATCAGTTGTGAG
TMPRSS DQ204773 2393 GAGGCGGAGGGCGAG 2394 TTCCTCGGGTCTCCAA 2395 CCTGGAATAACCTG 2396 GAGGCGGAGGGCGAGGGGCGGGGAGCGCCGCCTGGAGCG
2ERGB AGAT CCGCGC CGGCAGGTTATTCCAGGATCTTTGGAGACCCG
TNF NM_000594 2397 GGAGAAGGGTGAC 2398 TGCCCAGACTCGGCA 2399 CGCTGAGATCAATC 2400 GGAGAAGGGTGACCGACTCAGCGCTGAGATCAATCG
GGCCCG
TNFRSF1 NM_003844 2401 TGCACAGAGGGTGTG 2402 TCTTCATCTGATTTAC 2403 CAATGCTTCCAACA 2404 TGCACAGAGGGTGTGGGTTACACCAATGCTTCCAACAAT
0A GGTTAC AAGCTGTACATG ATTTGTTTGCTTGC TTGTTTGCTTGCCTCCCATGTACAGCTTGTAAAT
C
TNFRSF1 NM_003842 2405 CTCTGAGACAGTGCT 2406 CCATGAGGCCCAACTT 2407 CAGACTTGGTGCCC 2408 CTCTGAGACAGTGCTTCGATGACTTTGCAGACTTGGTTG
0B TCGATGACT CCT TTTGACTCC CCCTTTGACTCCTGGGAGCCGCTCATGAGGAAGTT
TNFRSF1 NM_148901 2409 CAGAAGCTGCCAGTT 2410 CACCCACAGGTCTCCC 2411 CCTTCTCCTCTGCC 2412 CAGAAGCTGCCAGTTCCCCGAGGAAGAGCGGGGCGAGCG
8 CCC AG GATCGCTC ATCGGCAGAGGAGAAGGGGCGGCTGGGAGACCT
TNFSF10 NM_003810 2413 CTTCACAGTGCTC 2414 CATCTGCTTCAGCTCG 2415 AAGTACACGTAAGT 2416 CTTCACAGTGCTCCTGCAGTCTCTCTGTGTGGCTGTA
TACAGC
TNFSF11 NM_003701 2417 AACTGCATGTGGG 2418 TGACACCCTCTCCACT 2419 ACATGACCAGGGAC 2420 AACTGCATGTGGGCTATGGGAGGGGTTGGTCCCTGG
CAACCC
TOP2A NM_001067 2421 AATCCAAGGGGGA 2422 GTACAGATTTTGCCC 2423 CATATGGACTTTG 2424 AATCCAAGGGGGAGAGTGATGACTTCCATATGGACT
ACTCAGC
TP53 NM_000546 2425 CTTTGAACCCTTGC 2426 CCCGGGACAAAGCAA 2427 AAGTCCTGGGTGC 2428 CTTTGAACCCTTGCTTGCAATAGGTGTGCGTCAGAAG
TTCTGAC
TP63 NM_003722 2429 CCCCAAGCAGTGC 2430 GAATCGCACAGCATC 2431 CCCGGGTCTCACT 2432 CCCCAAGCAGTGCCTCTACAGTCAGTGTGGGCTCCA
GGAGCCC
TPD52 NM_005079 2433 GCCTGTGAGATTC 2434 ATGTGCTTGGACCTC 2435 TCTGCTACCCACT 2436 GCCTGTGAGATTCCTACCTTTGTTCTGCTACCCACTG
GCCAGAT
TPM1 NM_001018005 2437 TCTCTGAGCTCTGCA 2438 GGCTCTAAGGCAGGAT 2439 TTCTCCAGCTGAC 2440 TCTCTGAGCTCTGCATTTGTCTATTCTCCAGCTGACCCT
TTTGTC GCTA CCTGGTTCTCTC GGTTCTCTCTCTTAGCATCCTGCTTAGAGCC
TPM2 NM_213674 2441 AGGAGATGCAGCT 2442 CCACCTCTTCATATTT 2443 CCAAGCACATCGC 2444 AGGAGATGCAGCTGAAGGAGGCCAAGCACATCGCTG
TGAGGAT
TPP2 NM_003291 2445 TAACCGTGGCATC 2446 ATGCCAACGCCATGA 2447 ATCCTGTTCAGGT 2448 TAACCGTGGCATCTACCTCCGAGATCCTGTTCAGGTG
GGCTGCA
TPX2 NM_012112 2449 TCAGCTGTGAGCTGC 2450 ACGGTCCTAGGTTTGA 2451 CAGGTCCCATTGC 2452 TCAGCTGTGAGCTGCGGATACCGCCCGGCAATGGGACCT
GGATA GGTTAAGA CGGGCG GCTCTTAACCTCAAACCTAGGACCGT
TRA2A NM_013293 2453 GCAAATCCAGATC 2454 CTTCACGAAGATCCC 2455 AACTGAGGCCAAA 2456 GCAAATCCAGATCCCAACACTTGCCTTGGAGTGTTTG
CACTCCA
TRAF31P NM_147200 2457 CCTCACAGGAACC 2458 CTGGGGCTGGGAATC 2459 TGGATCTGCCAAC 2460 CCTCACAGGAACCGAGCAGGCCTGGATCTGCCAACC
CATAGAC
TRAM1 NM_014294 2461 CAAGAAAAGCACC 2462 ATGTCCGCGTGATTCT 2463 AGTGCTGAGCCAC 2464 CAAGAAAAGCACCAAGAGCCCCCCAGTGCTGAGCCA
GAATTCG
TRAP1 NM_016292 2465 TTACCAGTGGCTTT 2466 TGTCCCGGTTCTAACT 2467 TTCGGCGATTTCA 2468 TTACCAGTGGCTTTCAGATGGTTCTGGAGTGTTTGAA
AACACTC
TRIM14 NM_033220 2469 CATTCGCCTTAAG 2470 CAAGGTACCTGGCTT 2471 AACTGCCAGCTCT 2472 CATTCGCCTTAAGGAAAGCATAAACTGCCAGCTCTCA
CAGACCC
TRO NM_177556 2473 GCAACTGCCACCC 2474 TGGTGTGGATACTGG 2475 CCACCCAAGGCCAA 2476 GCAACTGCCACCCATACAGCTACCACCCAAGGCCAA
ATTACC
TRPC6 NM_004621 2477 CGAGAGCCAGGACTA 2478 TAGCCGTAGCAAGGCA 2479 CTTCTCCCAGCTCC 2480 CGAGAGCCAGGACTATCTGCTCATGGACTCGGAGCTGGG
TCTGC GC GAGTCCATG AGAAGACGGCTGCCCGCAAGCCCCGCTGCCTTG
TRPV6 NM_018646 2481 CCGTAGTCCCTGCAA 2482 TCCTCACTGTTCACAC 2483 ACTTTGGGGAGCAC 2484 CCGTAGTCCCTGCAACCTCATCTACTTTGGGGAGCACCC
CCTC AGGC CCTTTGTCCT TTTGTCCTTTGCTGCCTGTGTGAACAGTGAGGA
TSTA3 NM_003313 2485 CAATTTGGACTTCT 2486 CACCTCAAAGGCCGA 2487 AACGTGCACATGAA 2488 CAATTTGGACTTCTGGAGGAAAAACGTGCACATGAA
CGACAA
TUBB2A NM_001069 2489 CGAGGACGAGGCT 2490 ACCATGCTTGAGGAC 2491 TCTCAGATCAATCG 2492 CGAGGACGAGGCTTAAAAACTTCTCAGATCAATCGT
TGCATC
TYMP NM_001953 2493 CTATATGCAGCCAGA 2494 CCACGAGTTTCTTACT 2495 ACAGCCTGCCACTC 2496 CTATATGCAGCCAGAGATGTGACAGCCACCGTGGACAGC
GATGTGACA GAGAATGG ATCACAGCC CTGCCACTCATCACAGCCTCCATTCTCAGTAAGA
TYMS NM_001071 2497 GCCTCGGTGTGCC 2498 CGTGATGTGCGCAAT 2499 CATCGCCAGCTACG 2500 GCCTCGGTGTGCCTTTCAACATCGCCAGCTACGCCCT
CCCTGC
UAP1 NM_003115 2501 CTGGAGACGGTCGTA 2502 GCCAAGCTTTGTAGAA 2503 TACCTGTAAACCTT 2504 CTGGAGACGGTCGTAGCTGCGGTCGCGCCGAGAAAGGTT
GCTG ATAGGG TCTCGGCGCG TACAGGTACATACATTACACCCCTATTTCTACAA
UBE2C NM_007019 2505 TGTCTGGCGATAA 2506 ATGGTCCCTACCCATT 2507 TCTGCCTTCCCTGA 2508 TGTCTGGCGATAAAGGGATTTCTGCCTTCCCTGAATC
ATCAGA
UBE2G1 NM_003342 2509 TGACACTGAACGA 2510 AAGCAGAGAGGAATC 2511 TTGTCCCACCAGTG 2512 TGACACTGAACGAGGTGGCTTTTGTCCCACCAGTGCC
CCTCAT
UBE2T NM_014176 2513 TGTTCTCAAATTGC 2514 AGAGGTCAACAAGT 2515 AGGTGCTTGGAGAC 2516 TGTTCTCAAATTGCCACCAAAAGGTGCTTGGAGACC
CATCCC
UGDH NM_003359 2617 GAAACTCCAGAGG 2518 CTCTGGGAACCCAGT 2519 TATACAGCACACAG 2520 GAAACTCCAGAGGGCCAGAGAGCTGTGCAGGCCCTG
GGCCTG
UGT2B1 NM_001076 2521 AAGCCTGAAGTGG 2522 CCTCCATTTAAAACCC 2523 AAAGATGGGACTCC 2524 AAGCCTGAAGTGGAATGACTGAAAGATGGGACTCCT
TCCTTT
UGT2B1 NM_001077 2525 TTGAGTTTGTCATG 2526 TCCAGGTGAGGTTGT 2527 ACCCGAAGGTGCTT 2528 TTGAGTTTGTCATGCGCCATAAAGGAGCCAAGCACC
GGCTCC
UHRF1 NM_013282 2529 CTACAGGGGCAAA 2530 GGTGTCATTCAGGCG 2531 CGGCCATACCCTCT 2532 CTACAGGGGCAAACAGATGGAGGACGGCCATACCCT
TCGACT
UTP23 NM_032334 2533 GATTGCACAAAAA 2534 GGAAAGCAGACATTC 2535 TCGAAATTGTCCTC 2536 GATTGCACAAAAATGCCAAGTTCGAAATTGTCCTCAT
ATTTCA
VCAM1 NM_001078 2537 TGGCTTCAGGAGCTG 2538 TGCTGTCGTGATGAGA 2539 CAGGCACACACAGG 2540 TGGCTTCAGGAGCTGAATACCCTCCCAGGCACACACAGG
AATACC AAATAGTG TGGGACACAAAT TGGGACACAAATAAGGGTTTTGGAACCACTATT
VCL NM_003373 2541 GATACCACAACTCCC 2542 TCCCTGTTAGGCGCAT 2543 AGTGGCAGCCACGG 2544 GATACCACAACTCCCATCAAGCTGTTGGCAGTGGCAGCC
ATCAAGCT CAG CGCC ACGGCGCCTCCTGATGCGCCTAACAGGGA
VCPIP1 NM_025054 2545 TTTCTCCCAGTACC 2546 TGAATAGGGAGCCTT 2547 TGGTCCATCCTCTG 2548 TTTCTCCCAGTACCATTCGTGATGGTCCATCCTCTGC
CACCTG
VDR NM_000376 2549 CCTCTCCTTCCAGC 2550 TCATTGCCAAACACTT 2551 CAGCATGAAGCTAA 2552 CCTCTCCTTCCAGCCTGAGTGCAGCATGAAGCTAACG
CGCCCC
VEGFA NM_003376 2553 CTGCTGTCTTGGG 2554 GCAGCCTGGGACCAC 2555 TTGCCTTGCTGCTC 2556 CTGCTGTCTTGGGTGCATTGGAGCCTTGCCTTGCTGC
TACCTC
VEGFB NM_003377 2557 TGACGATGGCCTG 2558 GGTACCGGATCATGA 2559 CTGGGCAGCACCAA 2560 TGACGATGGCCTGGAGTGTGTGCCCACTGGGCAGCA
GTCCGG
VEGFC NM_005429 2561 CCTCAGCAAGACGTT 2562 AAGTGTGATTGGCAAA 2563 CCTCTCTCTCAAGG 2564 CCTCAGCAAGACGTTATTTGAAATTACAGTGCCTCTCTC
ATTTGAAATT ACTGATTG CCCCAAACCAGT TCAAGGCCCCAAACCAGTAACAATCAGTTTTGCCA
VIM NM_003380 2565 TGCCCTTAAAGGA 2566 GCTTCAACGGCAAAG 2567 ATTTCACGCATCTG 2568 TGCCCTTAAAGGAACCAATGAGTCCCTGGAACGCCA
GCGTTC
VTI1B NM_006370 2569 ACGTTATGCACCCCT 2570 CCGATGGAGTTTAGCA 2571 CGAAACCCCATGAT 2572 ACGTTATGCACCCCTGTCTTTCCGAAACCCCATGATGTC
GTCTT AGGT GTCTAAGCTTCG TAAGCTTCGAAACTACCGGAAGGACCTTGCTAAA
WDR19 NM_025132 2573 GAGTGGCCCAGAT 2574 GATGCTTGAGGGCTT 2575 CCCCTCGACGTATG 2576 GAGTGGCCCAGATGTCCATAAGAATGGGAGACATAC
TCTCCC
WFDC1 NM_021197 2577 ACCCCTGCTCTGT 2578 ATACCTTCGGCCACG 2579 CTATGAGTGCCACA 2580 ACCCCTGCTCTGTCCCTCGGGCTATGAGTGCCACATC
TCCTGA
WISP1 NM_003882 2581 AGAGGCATCCATGAA 2582 CAAACTCCACAGTACT 2583 CGGGCTGCATCAGC 2584 AGAGGCATCCATGAACTTCACACTTGCGGGCTGCATCAG
CTTCACA TGGGTTGA ACACGC GCACACGCTCCTATCAACCCAAGTACTGTGGAGTT
WNT5A NM_003392 2585 GTATCAGGACCACAT 2586 TGTCGGAATTGATACT 2587 TTGATGCCTGTCTT 2588 GTATCAGGACCACATGCAGTACATCGGAGAAGGCGCGAA
GCAGTACATC GGCATT CGCGCCTTCT GACAGGCATCAAAGAATGCCAGTATCAATTCCG
WWOX NM_016373 2589 ATCGCAGCTGGTG 2590 AGCTCCCTGTTGCAT 2591 CTGCTGTTTACCTT 2592 ATCGCAGCTGGTGGGTGTACACACTGCTGTTTACCTT
GGCGAG
XIAP NM_001167 2593 GCAGTTGGAAGACAC 2594 TGCGTGGCACTATTTT 2595 TCCCCAAATTGCAG 2596 GCAGTTGGAAGACACAGGAAAGTATCCCCAAATTGCAGA
AGGAAAGT CAAGA ATTTATCAACGGC TTTATCAACGGCTTTTATCTTGAAAATAGTGCCA
XRCC5 NM_021141 2597 AGCCCACTTCAGC 2598 AGCAGGATTCACACT 2599 TCTGGCTGAAGGCA 2600 AGCCCACTTCAGCGTCTCCAGTCTGGCTGAAGGCAG
GTGTCA
YY1 NM_003403 2601 ACCCGGGCAACAA 2602 GACCGAGAACTCGCC 2603 TTGATCTGCACCTG 2604 ACCCGGGCAACAAGAAGTGGGAGCAGAAGCAGGTGC
CTTCTG
ZFHX3 NM_006885 2605 CTGTGGAGCCTCT 2606 GGAGCAGGGTTGGAT 2607 ACCTGGCCCAACTC 2608 CTGTGGAGCCTCTGCCTGCGGACCTGGCCCAACTCTA
TACCAG
ZFP36 NM_003407 2609 CATTAACCCACTC 2610 CCCCCACCATCATGA 2611 CAGGTCCCCAAGTG 2612 CATTAACCCACTCCCCTGACCTCACGCTGGGGCAGGT
TGCAAG
ZMYND8 NM_183047 2613 GGTCTGGGCCAAA 2614 TGCCCGTCTTTATCCC 2615 CTTTTGCAGGCCAG 2616 GGTCTGGGCCAAACTGAAGGGGTTTCCATTCTGGCCT
AATGGA
ZNF3 NM_017715 2617 CGAAGGGACTCTG 2618 GCAGGAGGTCCTCAG 2619 AGGAGGTTCCACAC 2620 CGAAGGGACTCTGCTCCAGTGAACTGGCGAGTGTGG
TCGCCA
ZNF827 NM_178835 2621 TGCCTGAGGACCC 2622 GAGGTGGCGGAGTGA 2623 CCCGCCTTCAGAGA 2624 TGCCTGAGGACCCTCTACCGCCCCCGCCTTCAGAGA
AGAAAC
ZWINT NM_007057 2625 TAGAGGCCATCAA 2626 TCCGTTTCCTCTGGGC 2627 ACCAAGGCCCTGAC 2628 TAGAGGCCATCAAAATTGGCCTCACCAAGGCCCTGA
TCAGAT
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 UG UAAACAUCCUCGACUGGAAG 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
