Gene signatures for cancer prognosis
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. A method for treating a prostate cancer patient having an increased likelihood of cancer recurrence or cancer-specific death, the method comprising:
(1) measuring, in a prostate cancer sample obtained from said prostate cancer patient, the mRNA expression levels of a panel of genes comprising at least 3 test genes selected from Panel F, wherein one of the at least 3 test genes is MCM10, and wherein the test genes of Panel F are 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;
(2) providing a test expression score by determining expression of each gene in said panel of genes and incorporating the expression of each gene in said panel of genes into said test expression score;
(3) providing a test prognostic score combining said test expression score with at least one test clinical score representing at least one clinical variable, wherein the test prognostic score is calculated according to a formula comprising the following terms: (A×test expression score)+(B×clinical score), wherein A=0.58, said clinical score is CAPRA score, and B=0.41;
(4) prognosing said prostate cancer patient as having an increased likelihood of cancer recurrence or cancer-specific death based at least in part on said test prognostic score exceeding a reference prognostic score; and
(5) administering one or more of hormonal therapy, chemotherapy, radiation therapy or surgery to said prostate cancer patient prognosed as having an increased likelihood of cancer recurrence or cancer-specific death.
2. The method of claim 1 , wherein said prognostic scores incorporate (a) a first clinical score representing preoperative PSA concentration, incorporated as a numerical concentration of ng/dL transformed by the natural logarithm, adding 1 to avoid zero values; and (b) a second clinical score representing a Gleason score, incorporated as a continuous numeric variable or categorized as <7 (reference level), 7, or >7.
3. The method of claim 1 , wherein one of the at least 3 test genes is DLGAP5.
4. A method for treating a prostate cancer patient having an increased likelihood of cancer recurrence or cancer-specific death, the method comprising:
(1) measuring, in a prostate cancer sample obtained from said prostate cancer patient, the mRNA expression levels of a panel of genes comprising at least 3 test genes selected from Panel F, wherein one of the at least 3 test genes is MCM10, and wherein the test genes of Panel F are 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;
(2) providing a test expression score by determining expression of each gene in said panel of genes and incorporating the expression of each gene in said panel of genes into said test expression score;
(3) providing a test prognostic score combining said test expression score with at least one test clinical score representing at least one clinical variable, wherein the test prognostic score is calculated according to a formula comprising the following terms: (A×test expression score)+(B×clinical score), wherein A=0.58, said clinical score is CAPRA score, and B=0.41;
(4) prognosing said prostate cancer patient as having no increased likelihood of cancer recurrence or cancer-specific death based at least in part on said test prognostic score not exceeding a reference prognostic score;
(5) administering active surveillance to said prostate cancer patient prognosed as having no increased likelihood of cancer recurrence or cancer-specific death; and
(6) further administering one or more of hormonal therapy, chemotherapy, radiation therapy or surgery to said prostate cancer patient based on the presence of prostate cancer symptoms and/or signs of accelerated prostate cancer growth to said prostate cancer patient administered active surveillance.