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 . 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.