Gene signatures for cancer prognosis

Abstract

Biomarkers and methods using the biomarkers for the prediction of the recurrence risk of cancer in a patient are provided.

1 . A method of determining gene expression in a tumor sample, comprising:
 obtaining a tumor sample from a patient identified as having prostate cancer, lung cancer, bladder cancer or brain cancer;   determining the expression levels of a panel of genes in said tumor sample including at least 4 cell-cycle genes listed in Table 1; and   providing a test value by (1) weighting the determined expression of each of a plurality of test genes selected from said panel of genes with a predefined coefficient, and (2) combining the weighted expression to provide said test value, wherein said at least 4 cell-cycle genes listed in Table 1 are at least 75% of said plurality of test genes.   
     
     
         2 . The method of  claim 1 , wherein at least 90% of said plurality of test genes are cell-cycle genes listed in Table 1. 
     
     
         3 . The method of  claim 1 , wherein said determining step comprises:
 measuring the amount of mRNA in said tumor sample transcribed from each of between 6 and 200 cell-cycle genes listed in Table 1; and   measuring the amount of mRNA of one or more housekeeping genes in said tumor sample.   
     
     
         4 . The method of  claim 1 , wherein the expression of at least 8 cell-cycle genes listed in Table 1 are determined and weighted. 
     
     
         5 . A method of prognosing prostate cancer, lung cancer, bladder cancer or brain cancer, comprising:
 determining, in a tumor sample from a patient diagnosed of prostate cancer, lung cancer, bladder cancer or brain cancer, the expression of a panel of genes comprising at least 4 cell-cycle genes listed in Table 1;   providing a test value by (1) weighting the determined expression of each of a plurality of test genes selected from said panel of genes with a predefined coefficient, and (2) combining the weighted expression to provide said test value, wherein said at least 4 cell-cycle genes listed in Table 1 are at least 75% of said plurality of test genes; and   correlating an increased level of expression of said plurality of test genes to a poor prognosis.   
     
     
         6 . The prognosis method of  claim 5 , further comprising comparing said test value to a reference value, and correlating to an increased likelihood of poor prognosis if said test value is greater than said reference value. 
     
     
         7 . The prognosis method of  claim 5 , wherein the expression levels of from 6 to about 200 cell-cycle genes listed in Table 1 are measured. 
     
     
         8 . (canceled) 
     
     
         9 . A method of treating cancer in a patient identified as having prostate cancer, lung cancer, bladder cancer or brain cancer, comprising:
 determining in a tumor sample from a patient diagnosed of prostate cancer, lung cancer, bladder cancer or brain cancer, the expression of a panel of genes comprising at least 4 cell-cycle genes listed in Table 1;   providing a test value by (1) weighting the determined expression of each of a plurality of test genes selected from said panel of genes with a predefined coefficient, and (2) combining the weighted expression to provide said test value, wherein said at least 4 cell-cycle genes listed in Table 1 are at least 75% of said plurality of test genes, and wherein an increased level of expression of said plurality of test genes indicates a poor prognosis; and   administering to said patient an anti-cancer drug, or recommending or prescribing or initiating active treatment if a poor prognosis is indicated.   
     
     
         10 - 23 . (canceled) 
     
     
         24 . A system for prognosing cancer selected from lung cancer or colon cancer, comprising:
 (1) a sample analyzer for determining the expression levels of a panel of genes comprising at least 4 cell-cycle genes listed in Table 1 in a tumor sample from a patient identified as having lung cancer or colon cancer, wherein the sample analyzer contains the tumor sample, RNA expressed from the panel of genes, or DNA synthesized from such RNA; and   (2) a first computer subsystem programmed for (a) receiving gene expression data on a plurality of at least 4 test genes selected from the panel of genes, (b) weighting the determined expression of each of the test genes, and (c) combining the weighted expression to provide a test value, wherein the combined weight given to said at least 4 cell-cycle genes listed in Table 1 is at least 40% of the total weight given to the expression of all of said plurality of at least 4 test genes; and   (3) a second computer subsystem programmed for comparing the test value to one or more reference values each associated with a predetermined degree of risk of cancer recurrence or progression of the lung cancer or colon cancer.   
     
     
         25 . The system of  claim 24 , further comprising a display module displaying the comparison between the test value to the one or more reference values, or displaying a result of the comparing step. 
     
     
         26 . (canceled) 
     
     
         27 . A method for determining gene expression in a tumor sample, comprising:
 determining, in a tumor sample from a patient diagnosed of prostate cancer, lung cancer, bladder cancer or brain cancer, the expression of a panel of genes comprising at least 4 cell-cycle genes listed in Table 1;   providing a test value by weighting the determined expression of each of a plurality of test genes selected from said panel of genes with a predefined coefficient, wherein the combined weight given to said at least 4 cell-cycle genes listed in Table 1 is at least 40% of the total weight given to the expression of all of said plurality of test genes.