Gene signatures for cancer prognosis

Abstract

Biomarkers and methods using the biomarkers for classifying cancer in a patient (e.g., predicting the risk of cancer-specific death or cancer recurrence) are provided.

1 - 63 . (canceled) 
     
     
         64 . A method for detecting the risk of a recurring prostate cancer, lung cancer, bladder cancer, brain cancer, or breast cancer in a patient, the method comprising:
 measuring in a sample obtained from the patient expression levels of at least three genes of a panel of genes comprising ASF1B, ASPM, BIRC5, BUB1B, C18orf24, CDC2, CDC20, CDCA3, CDCA8, CDKN3, CENPF, CENPM, CEP55, DLGAP5, DTL, FOXM1, KIAA0101, KIF11, KIF20A, MCM10, NUSAP1, ORC6L, PBK, PLK1, PRC1, PTTG1, RAD51, RAD54L, RRM2, TK1 and TOP2A, along with expression levels of any one or more genes comprising KLK3, PCA3, ERG, TMPRSS2, STX4, TAF5L, GTPBP5, SIRT3, EIF3D, LOC100126784, ABCG1, CYP1B1-AS1, and CECR6;   providing a test expression score by
 (a) weighting the determined expression of each of the genes, and 
 (b) combining the weighted expression of each of the genes to provide the test expression score, wherein the at least three genes of the panel are weighted to contribute at least 25% to the test expression score; and 
   prognosing, before recurrence of the cancer, the patient as having an increased likelihood of cancer recurrence or cancer-specific death based on the test expression score showing elevated progression risk of the cancer.   
     
     
         65 . The method of  claim 64 , wherein expression levels are normalized to expression of housekeeping genes. 
     
     
         66 . The method of  claim 64 , wherein the at least three genes of the panel are weighted to contribute at least 80% to the test expression score. 
     
     
         67 . The method of  claim 64 , wherein at least 75% of the genes are cell cycle genes. 
     
     
         68 . The method of  claim 64 , wherein expression is measured as the amount of mRNA in the sample for each gene, or the amount of cDNA reverse transcribed from mRNA of each gene. 
     
     
         69 . The method of  claim 64 , wherein cancer recurrence or cancer-specific death is from distant metastasis of the primary cancer, local metastasis of the primary cancer, recurrence of the primary cancer, progression of the primary cancer, or development of locally advanced, metastatic disease. 
     
     
         70 . The method of  claim 64 , wherein the sample is a tumor or biopsy sample. 
     
     
         71 . The method of  claim 64 , wherein the prognosing combines the weighted expressions of the genes with binary clinical parameters. 
     
     
         72 . The method of  claim 71 , wherein one of the binary clinical parameters is organ-confined disease. 
     
     
         73 . The method of  claim 64 , further comprising, after the prognosing, active surveillance of the patient for a period of time until symptoms develop or there are signs that the cancer growth is accelerating. 
     
     
         74 . A method for prognosing a rate of progression of a recurring prostate cancer, lung cancer, bladder cancer, brain cancer, or breast cancer in a patient, the method comprising:
 measuring in a sample obtained from the patient expression levels of at least three genes of a panel of genes comprising ASF1B, ASPM, BIRC5, BUB1B, C18orf24, CDC2, CDC20, CDCA3, CDCA8, CDKN3, CENPF, CENPM, CEP55, DLGAP5, DTL, FOXM1, KIAA0101, KIF11, KIF20A, MCM10, NUSAP1, ORC6L, PBK, PLK1, PRC1, PTTG1, RAD51, RAD54L, RRM2, TK1 and TOP2A, along with expression levels of any one or more genes comprising KLK3, PCA3, ERG, TMPRSS2, STX4, TAF5L, GTPBP5, SIRT3, EIF3D, LOC100126784, ABCG1, CYP1B1-AS1, and CECR6;   providing a test expression score by
 (a) weighting the determined expression of each of the genes, and 
 (b) combining the weighted expression of each of the genes to provide the test expression score, wherein the at least three genes of the panel are weighted to contribute at least 25% to the test expression score; and 
   prognosing, before recurrence of the cancer, the patient as having an increased likelihood of cancer recurrence or cancer-specific death based on the test expression score showing the rate of progression of the cancer.   
     
     
         75 . The method of  claim 74 , wherein expression levels are normalized to expression of housekeeping genes. 
     
     
         76 . The method of  claim 74 , wherein the at least three genes of the panel are weighted to contribute at least 50% to the test expression score. 
     
     
         77 . The method of  claim 74 , wherein the at least three genes of the panel are weighted to contribute at least 80% to the test expression score. 
     
     
         78 . The method of  claim 74 , wherein at least 75% of the genes are cell cycle genes. 
     
     
         79 . The method of  claim 74 , wherein expression is measured as the amount of mRNA in the sample for each gene, or the amount of cDNA reverse transcribed from mRNA of each gene. 
     
     
         80 . The method of  claim 74 , wherein cancer recurrence or cancer-specific death is from distant metastasis of the primary cancer, local metastasis of the primary cancer, recurrence of the primary cancer, progression of the primary cancer, or development of locally advanced, metastatic disease. 
     
     
         81 . The method of  claim 74 , wherein the sample is a tumor sample. 
     
     
         82 . The method of  claim 74 , wherein the prognosing combines the weighted expressions of the genes with binary clinical parameters. 
     
     
         83 . The method of  claim 82 , wherein one of the binary clinical parameters is organ-confined disease.