METHOD FOR USING GENE EXPRESSION TO DETERMINE PROGNOSIS OF PROSTATE CANCER

Molecular assays that involve measurement of expression levels of prognostic biomarkers, or co-expressed biomarkers, from a biological sample obtained from a prostate cancer patient, and analysis of the measured expression levels to provide information concerning the likely prognosis for said patient, and likelihood that said patient will have a recurrence of prostate cancer, or to classify the tumor by likelihood of clinical outcome or TMPRSS2 fusion status, are provided herein.

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Description

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

Claims

1. A method for determining a likelihood of cancer recurrence in a patient with prostate cancer, comprising:

measuring an expression level of at least one gene in a biological sample comprising prostate tissue obtained from the patient, wherein the at least one gene comprises a gene from Tables 3A, 3B, 4A, 4B, 5A, 5B, 6A, 6B, 7A, 7B, 8A, 8B, 10A, or 10B, or genes that co-express with the at least one gene;
predicting a likelihood of cancer recurrence for the patient; wherein an expression level of any gene in Tables 3A, 4A, 5A, 6A, 7A, 8A, and 10A is positively associated with an increased risk of recurrence, and wherein an expression level of any gene in Tables 3B, 4B, 5B, 6B, 7B 8B, and 10B is negatively associated with a increased risk of recurrence.

2. The method of claim 1, wherein said expression level is measured using an RNA transcript of the at least one gene.

3. The method of claim 1, wherein said expression is measured using an oligonucleotide associated with the at least one gene.

4. The method of claim 1, further comprising normalizing said expression level to obtain a normalized expression level.

5. The method of claim 1, further comprising generating a report based on the Recurrence Score (RS).

6. The method of claim 5, wherein the report comprises an estimate of recurrence risk based on clinical recurrence-free interval (cRFI).

7. The method of claim 5, wherein the RS is based on a biochemical recurrence-free interval (bRFI).

8. The method of claim 1, wherein the biological sample has a positive TMPRSS2 fusion status.

9. The method of claim 1, wherein the biological sample has a negative TMPRSS2 fusion status.

10. The method of claim 1, wherein the patient has early-stage prostate cancer.

11. The method of claim 1, wherein the biological sample comprises prostate tumor tissue with the primary Gleason pattern for said prostate tumor.

12. The method of claim 1, wherein the biological samples comprises prostate tumor tissue with the highest Gleason pattern for said prostate tumor.

13. The method of claim 1, wherein the biological sample is prostate tumor tissue.

14. The method of claim 1, wherein the biological sample is non-tumor prostate tissue.

15. The method of claim 1, further comprising classifying the patient as TMPRSS2 fusion positive or negative,

wherein an expression level of any gene in Table 9A is associated with a positive TMPRSS2 fusion status, and
wherein an expression level of any gene in Table 9B is associated with a negative TMPRSS2 fusion status.

16. The method of claim 1, wherein the biological sample comprises non-tumor prostate tissue, and wherein the at least one gene comprises a gene from Tables 10A or 10B.

17. A method for determining a likelihood of upgrading or upstaging in a patient with prostate cancer, comprising:

measuring an expression level of at least one gene in a biological sample comprising prostate tissue obtained from the patient, wherein the at least one gene comprises a gene from Table 13A or 13B, or genes that co-express with the at least one gene;
wherein an expression level of any gene in Tables 13A is positively associated with an increased risk of upgrading/upstaging, and
wherein an expression level of any gene in Table 13B is negatively associated with a increased risk of upgrading/upstaging.

18. A method for determining a likelihood of cancer recurrence in a patient with prostate cancer, comprising:

measuring an expression level of at least one microRNA in a biological sample comprising prostate tissue obtained from the patient, wherein the at least one microRNA is a microRNA selected from 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; hsa-miR-200c; 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; and
normalizing said expression level to obtain a normalized expression level;
wherein a normalized expression level 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 is positively associated with an increased risk of recurrence; and
wherein a normalized expression level of 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 is negatively associated with an increased risk of recurrence.

19. The method of claim 18, further comprising measuring an expression level of at least one gene in said biological sample.

20. The method of claim 19, wherein the at least one gene is a gene selected from Tables 3A, 3B, 4A, 4B, 5A, 5B, 6A, 6B, 7A, 7B, 8A, 8B, 10A, or 10B, or genes that co-express with the at least one gene;

wherein an expression level of any gene in Tables 3A, 4A, 5A, 6A, 7A, 8A, and 10A is positively associated with an increased risk of recurrence, and
wherein an expression level of any gene in Tables 3B, 4B, 5B, 6B, 7B 8B, and 10B is negatively associated with a increased risk of recurrence.
Patent History
Publication number: 20120028264
Type: Application
Filed: Jul 25, 2011
Publication Date: Feb 2, 2012
Inventors: Steven Shak (Hillsborough, CA), Frederick L. Baehner (San Francisco, CA), Tara Maddala (Sunnyvale, CA), Mark Lee (Los Altos Hills, CA), Robert J. Pelham (Belmont, CA), Wayne Cowens (Tiburon, CA), Diana Cherbavaz (San Francisco, CA), Michael C. Kiefer (Walnut Creek, CA), Michael Crager (Menlo Park, CA), Audrey Goddard (San Francisco, CA), Joffre B. Baker (Montara, CA)
Application Number: 13/190,391