Method for Using Gene Expression to Determine Prognosis of Prostate Cancer

Abstract

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.

1 .- 20 . (canceled) 
     
     
         21 . A method of analyzing expression of RNA transcripts of genes in a patient with prostate cancer, comprising:
 measuring a level of an RNA transcript, in a sample from the patient comprising prostate tumor tissue, of a set of genes consisting of: (a) at least one gene selected from the group consisting of genes listed in Table 3A; and (b) at least one gene selected from the group consisting of genes listed in Table 3B; and (c) at least one reference gene.   
     
     
         22 . The method of  claim 21 , wherein the at least one gene selected from the group consisting of genes listed in Table 3A includes at least one of BGN, COL1A1, SFRP4, and TPX2. 
     
     
         23 . The method of  claim 22 , wherein the RNA transcript level of the at least one of BGN, COL1A1, SFRP4, and TPX2 is measured using at least one of the following sets of oligonucleotides:
 SEQ ID Nos: 257, 258, and 259 (for BGN);   SEQ ID Nos: 501, 502, and 503 (for COL1A1);   SEQ ID Nos: 2157, 2158, and 2159 (for SFRP4); and   SEQ ID Nos: 2449, 2450, and 2451 (for TPX2).   
     
     
         24 . The method of  claim 21 , wherein the at least one gene selected from the group consisting of genes listed in Table 3B includes at least one of FLNC, GSN, GSTM2, TPM2, AZGP1, KLK2, FAM13C, and SRD5A2. 
     
     
         25 . The method of  claim 24 , wherein the RNA transcript level of the at least one of FLNC, GSN, GSTM2, TPM2, AZGP1, KLK2, FAM13C, and SRD5A2 is measured using at least one of the following sets of oligonucleotides:
 SEQ ID Nos: 929, 930, and 931 (for FLNC);   SEQ ID Nos: 1029, 1030, and 1031 (for GSN);   SEQ ID Nos: 1037, 1038, and 1039 (for GSTM2);   SEQ ID Nos: 2441, 2442, and 2443 (for TPM2);   SEQ ID Nos: 225, 226, and 227 (for AZGP1);   SEQ ID Nos: 1361, 1362, and 1363 (for KLK2);   SEQ ID Nos: 857, 858, and 859 (for FAM13C); and   SEQ ID Nos: 2273, 2274, and 2275 (for SRD5A2).   
     
     
         26 . The method of  claim 21 , wherein the at least one gene selected from the group consisting of genes listed in Table 3A includes at least one of BGN, COL1A1, SFRP4, and TPX2; and wherein the at least one gene selected from the group consisting of genes listed in Table 3B includes at least one of FLNC, GSN, GSTM2, TPM2, AZGP1, KLK2, FAM13C, and SRD5A2. 
     
     
         27 . The method of  claim 26 , wherein the RNA transcript level of the at least one of BGN, COL1A1, SFRP4, and TPX2 is measured using at least one of the following sets of oligonucleotides:
 SEQ ID Nos: 257, 258, and 259 (for BGN);   SEQ ID Nos: 501, 502, and 503 (for COL1A1);   SEQ ID Nos: 2157, 2158, and 2159 (for SFRP4); and   SEQ ID Nos: 2449, 2450, and 2451 (for TPX2); and   wherein the RNA transcript level of the at least one of FLNC, GSN, GSTM2, TPM2, AZGP1, KLK2, FAM13C, and SRD5A2 is measured using at least one of the following sets of oligonucleotides:   SEQ ID Nos: 929, 930, and 931 (for FLNC);   SEQ ID Nos: 1029, 1030, and 1031 (for GSN);   SEQ ID Nos: 1037, 1038, and 1039 (for GSTM2);   SEQ ID Nos: 2441, 2442, and 2443 (for TPM2);   SEQ ID Nos: 225, 226, and 227 (for AZGP1);   SEQ ID Nos: 1361, 1362, and 1363 (for KLK2);   SEQ ID Nos: 857, 858, and 859 (for FAM13C); and   SEQ ID Nos: 2273, 2274, and 2275 (for SRD5A2).   
     
     
         28 . The method of  claim 21 , wherein the at least one gene selected from the group consisting of genes listed in Table 3A includes each of BGN, COL1A1, SFRP4, and TPX2. 
     
     
         29 . The method of  claim 21 , wherein the at least one gene selected from the group consisting of genes listed in Table 3B includes each of FLNC, GSN, GSTM2, TPM2, AZGP1, KLK2, FAM13C, and SRD5A2. 
     
     
         30 . The method of  claim 21 , wherein the at least one gene selected from the group consisting of genes listed in Table 3A includes each of BGN, COL1A1, SFRP4, and TPX2; and wherein the at least one gene selected from the group consisting of genes listed in Table 3B includes each of FLNC, GSN, GSTM2, TPM2, AZGP1, KLK2, FAM13C, and SRD5A2. 
     
     
         31 . The method of  claim 21 , wherein the at least one reference gene is a gene that does not exhibit a significantly different RNA expression level in cancerous prostate tissue compared to non-cancerous prostate tissue. 
     
     
         32 . The method of  claim 21 , wherein the at least one reference gene consists of from 1 to 6 reference genes. 
     
     
         33 . The method of  claim 21 , wherein the at least one reference gene comprises one or more of AAMP, ARF1, ATP5E, CLTC, EEF1A1, GPS1, GPX1, and PGK1. 
     
     
         34 . The method of  claim 21 , wherein the biological sample has a positive TMPRSS2 fusion status. 
     
     
         35 . The method of  claim 21 , wherein the biological sample has a negative TMPRSS2 fusion status. 
     
     
         36 . The method of  claim 21 , wherein the patient has early-stage prostate cancer. 
     
     
         37 . The method of  claim 21 , wherein the biological sample comprises prostate tumor tissue with the primary Gleason pattern for said prostate tumor. 
     
     
         38 . The method of  claim 21 , wherein the biological samples comprises prostate tumor tissue with the highest Gleason pattern for said prostate tumor. 
     
     
         39 . The method of  claim 21 , wherein the tissue sample comprises non-tumor prostate tissue. 
     
     
         40 . The method of  claim 21 , wherein the patient is receiving active surveillance treatment.