Colorectal cancer recurrence gene expression signature

Abstract

Disclosed are gene signatures that may be used to predict the recurrence of colorectal cancer in a human patient. These signatures can be used to determine when to treat a patient with post-operative adjuvant chemotherapy, i.e., when a high risk of colorectal cancer recurrence is predicted.

1 . A method for predicting the recurrence of colorectal cancer in a human patient, comprising:
 (a) assaying colorectal cells obtained from the human patient for the expression level of ten (10) or more genes listed in TABLE 2A, or their corresponding expression products, and ten (10) or more genes listed in TABLE 2B, or their corresponding expression products, and using normalized values of the expression levels to calculate a colorectal cancer (CRC) score;   (b) assaying colorectal cells obtained from the human patient for the expression levels of ten (10) or more genes listed in TABLE 1A, or their corresponding expression products, and ten (10) or more genes listed TABLE 1B, or their corresponding expression products, and using normalized values of the expression levels to calculate an Epithelial to Mesenchymal Transition (EMT) score; and   (c) calculating the difference between the CRC score and the EMT score to arrive at a Recurrence Signature Score that predicts risk of colorectal cancer recurrence.   
     
     
         2 . The method of  claim 1 , further comprising displaying or outputting to a user, user interface device, computer readable storage medium, or local or remote computer system the calculated risk of colorectal cancer recurrence. 
     
     
         3 . The method of  claim 1 , further comprising treating the human patient with post-operative adjuvant chemotherapy if a high risk of colorectal cancer recurrence is determined. 
     
     
         4 . The method of  claim 3 , wherein the chemotherapy comprises a 5-fluorouracil (5-FU) therapy. 
     
     
         5 . The method of  claim 1 , wherein increased expression of the genes listed in TABLE 2A, or their corresponding expression products, increases the CRC score; and wherein increased expression of the genes listed in TABLE 2B, or their corresponding products, decreases the CRC score. 
     
     
         6 . The method of  claim 1 , wherein increased expression of the genes listed in TABLE 1A, or their corresponding expression products, increases the EMT score; and wherein increased expression of the genes listed in TABLE 1B, or their corresponding products, decreases the EMT score. 
     
     
         7 . The method of  claim 1 , wherein the expression levels are normalized by quantile normalization. 
     
     
         8 . The method of  claim 1 , wherein the normalized expression values of the expression levels for each assayed gene are given equal weight in calculating the CRC score. 
     
     
         9 . The method of  claim 1 , wherein the normalized expression values of the expression levels for each assayed gene are given equal weight in calculating the EMT score. 
     
     
         10 . The method of  claim 1 , wherein the colorectal cancer comprises Dukes B (stage II) or Dukes C (stage III) colorectal cancer. 
     
     
         11 . A method for analyzing a colorectal cancer tissue sample to determine adjuvant chemotherapy is needed to prevent colorectal cancer recurrence in a human patient, the method comprising:
 (a) assaying colorectal cells obtained from the human patient for normalized expression values of ten (10) or more genes listed in TABLE 1A, ten (10) or more genes listed in TABLE 1B, ten (10) or more genes listed in TABLE 2A, and ten (10) or more genes listed in TABLE 2B; and   (b) inputting the normalized expression values into a computer programmed to execute an algorithm to convert the normalized expression values to a Recurrence Signature Score indicative of a likelihood of the risk of colorectal cancer recurrence, wherein the algorithm gives reduced weight to the normalized expression values for genes that are listed in more than one of TABLE 1A, TABLE 1B, TABLE 1C, and TABLE 1D.   
     
     
         12 . The method of  claim 11 , wherein the algorithm converts the normalized expression values for the genes listed in TABLE 2A and TABLE 2B to a colorectal cancer (CRC) score, wherein the algorithm converts the normalized expression values for the genes listed in TABLE 1A and TABLE 1B to an Epithelial to Mesenchymal Transition (EMT) score, wherein the Recurrence Signature Score is determined by calculating the difference between the CRC score and the EMT score. 
     
     
         13 . The method of  claim 12 , wherein increased expression of the genes listed in TABLE 2A, or their corresponding expression products, increases the CRC score; and wherein increased expression of the genes listed in TABLE 2B, or their corresponding products, decreases the CRC score. 
     
     
         14 . The method of  claim 12 , wherein increased expression of the genes listed in TABLE 1A, or their corresponding expression products, increases the EMT score; and wherein increased expression of the genes listed in TABLE 1B, or their corresponding products, decreases the EMT score. 
     
     
         15 . The method of  claim 11 , further comprising treating the human patient with post-operative adjuvant chemotherapy if a high risk of colorectal cancer recurrence is determined. 
     
     
         16 . The method of  claim 15 , wherein the chemotherapy comprises a 5-fluorouracil (5-FU) therapy. 
     
     
         17 . The method of  claim 11 , wherein the expression levels are normalized by quantile normalization. 
     
     
         18 . The method of  claim 11 , wherein the normalized expression values of the expression levels for each assayed gene are given equal weight in calculating the CRC score. 
     
     
         19 . The method of  claim 11 , wherein the normalized expression values of the expression levels for each assayed gene are given equal weight in calculating the EMT score. 
     
     
         20 . The method of  claim 11 , wherein the colorectal cancer comprises Dukes B (stage II) or Dukes C (stage III) colorectal cancer.