• The lancet oncology · Nov 2012

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

    • Robert W Ross, Matthew D Galsky, Howard I Scher, Jay Magidson, Karl Wassmann, Gwo-Shu Mary Lee, Leah Katz, Sumit K Subudhi, Aseem Anand, Martin Fleisher, Philip W Kantoff, and William K Oh.
    • Division of Solid Tumor Oncology, Department of Medicine, Dana-Farber Cancer Institute, Boston, MA, USA.
    • Lancet Oncol. 2012 Nov 1; 13 (11): 1105-13.

    BackgroundSurvival 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.MethodsPeripheral 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.FindingsA 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).InterpretationTranscriptional 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.FundingSource MDX.Copyright © 2012 Elsevier Ltd. All rights reserved.

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