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 .- 17 . (canceled) 
     
     
         18 . A method for treating prostate cancer, lung cancer, bladder cancer, brain cancer or breast cancer in a patient in need, the method comprising:
 measuring in a cancer sample obtained from the patient expression levels of a panel of genes comprising at least three genes of a set 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;   calculating a test prognostic score combining the expression levels with a clinical variable of the patient;   prognosing the patient as having an increased likelihood of cancer recurrence or cancer-specific death based at least in part on the test prognostic score exceeding a reference prognostic score; and   administering one or more of hormonal therapy, chemotherapy, radiation therapy or surgery to the patient prognosed as having an increased likelihood of cancer recurrence or cancer-specific death.   
     
     
         19 . The method of  claim 18 , wherein the expression levels are weighted to contribute 30% to 100% of the total test prognostic score. 
     
     
         20 . The method of  claim 18 , wherein the panel of genes comprises at least four genes of the set of genes. 
     
     
         21 . The method of  claim 18 , wherein one of the at least three test genes is MCM10. 
     
     
         22 . The method of  claim 18 , wherein one of the at least three test genes is DLGAP5. 
     
     
         23 . The method of  claim 18 , wherein the panel of genes further comprises KLK3. 
     
     
         24 . The method of  claim 18 , wherein cancer recurrence is one of 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. 
     
     
         25 . The method of  claim 18 , wherein the clinical variable is a cancer nomogram score. 
     
     
         26 . The method of  claim 18 , wherein for prostate cancer the clinical variable is a Gleason score, a CAPRA nomogram score, or a Kattan-Stephenson nomogram score. 
     
     
         27 . The method of  claim 18 , wherein for prostate cancer the test prognostic score incorporates
 a first clinical variable representing preoperative PSA concentration, incorporated as a numerical concentration of ng/dL transformed by the natural logarithm, adding 1 to avoid zero values; and   a second clinical variable representing a Gleason score, incorporated as a continuous numeric variable or categorized as <7 (reference level), 7, or >7.   
     
     
         28 . A method for treating prostate cancer, lung cancer, bladder cancer, brain cancer or breast cancer in a patient in need, the method comprising:
 measuring in a cancer sample obtained from the patient expression levels of a panel of genes comprising at least three genes of a set 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;   calculating a test prognostic score combining the expression levels with a clinical variable of the patient;   prognosing the patient as having no increased likelihood of cancer recurrence or cancer-specific death based at least in part on the test prognostic not exceeding a reference prognostic score;   administering active surveillance to the cancer patient prognosed as having no increased likelihood of cancer recurrence or cancer-specific death; and   administering one or more of hormonal therapy, chemotherapy, radiation therapy or surgery to the patient based on the presence of cancer symptoms and/or signs of accelerated cancer growth in the patient who was administered active surveillance.   
     
     
         29 . The method of  claim 28 , wherein the expression levels are weighted to contribute 30% to 100% of the total test prognostic score. 
     
     
         30 . The method of  claim 28 , wherein the panel of genes comprises at least four genes of the set of genes. 
     
     
         31 . The method of  claim 28 , wherein one of the at least three test genes is MCM10. 
     
     
         32 . The method of  claim 28 , wherein one of the at least three test genes is DLGAP5. 
     
     
         33 . The method of  claim 28 , wherein the panel of genes further comprises KLK3. 
     
     
         34 . The method of  claim 28 , wherein cancer recurrence is one of 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. 
     
     
         35 . The method of  claim 18 , wherein the clinical variable is a cancer nomogram score. 
     
     
         36 . The method of  claim 18 , wherein for prostate cancer the clinical variable is a Gleason score, a CAPRA nomogram score, or a Kattan-Stephenson nomogram score. 
     
     
         37 . The method of  claim 28 , wherein for prostate cancer the test prognostic score incorporates
 a first clinical variable representing preoperative PSA concentration, incorporated as a numerical concentration of ng/dL transformed by the natural logarithm, adding 1 to avoid zero values; and   a second clinical variable representing a Gleason score, incorporated as a continuous numeric variable or categorized as <7 (reference level), 7, or >7.