A whole-blood RNA transcript-based prognostic model in men with castration-resistant prostate cancer: a prospective study

作者：Ross Robert W; Galsky Matthew D; Scher Howard I; Magidson Jay; Wassmann Karl; Lee Gwo Shu Mary; Katz Leah; Subudhi Sumit K; Anand Aseem; Fleisher Martin; Kantoff Philip W; Oh William K^*

来源：Lancet Oncology, 2012, 13(11): 1105-1113.

DOI：10.1016/S1470-2045(12)70263-2

Background Survival for patients with castration-resistant prostate cancer is highly variable. We assessed the effectiveness of a whole-blood RNA transcript-based model as a prognostic biomarker in castration-resistant prostate cancer.
Methods Peripheral blood was prospectively collected from 62 men with castration-resistant prostate cancer on various treatment regimens who were enrolled in a training set at the Dana-Farber Cancer Institute (Boston, MA, USA) from August, 2006, to June, 2008, and from 140 patients with castration-resistant prostate cancer in a validation set from Memorial Sloan-Kettering Cancer Center (New York, NY, USA) from August, 2006, to February, 2009. A panel of 168 inflammation-related and prostate cancer-related genes was assessed with optimised quantitative PCR to assess biomarkers predictive of survival.
Findings A six-gene model (consisting of ABL2, SEMA4D, ITGAL, and C1QA, TIMP1, CDKN1A) separated patients with castration-resistant prostate cancer into two risk groups: a low-risk group with a median survival of more than 34.9 months (median survival was not reached) and a high-risk group with a median survival of 7.8 months (95% CI 1.8-13.9; p<0.0001). The prognostic utility of the six-gene model was validated in an independent cohort. This model was associated with a significantly higher area under the curve compared with a clinicopathological model (0.90 [95% CI 0.78-0.96] vs 0.65 [0.52-0.78]; p=0.0067).
Interpretation Transcriptional profiling of whole blood yields crucial prognostic information about men with castration-resistant prostate cancer. The six-gene model suggests possible dysregulation of the immune system, a finding that warrants further study.
Funding Source MDX.

• 出版日期2012-11