TY - JOUR
T1 - A whole-blood RNA transcript-based prognostic model in men with castration-resistant prostate cancer
T2 - A prospective study
AU - Ross, Robert W.
AU - Galsky, Matthew D.
AU - Scher, Howard I.
AU - Magidson, Jay
AU - Magidson, Karl
AU - Lee, Gwo Shu Mary
AU - Katz, Leah
AU - Subudhi, Sumit K.
AU - Anand, Aseem
AU - Fleisher, Martin
AU - Kantoff, Philip W.
AU - Oh, William K.
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
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U2 - 10.1016/S1470-2045(12)70263-2
DO - 10.1016/S1470-2045(12)70263-2
M3 - Article
C2 - 23059047
AN - SCOPUS:84868208177
SN - 1470-2045
VL - 13
SP - 1105
EP - 1113
JO - The lancet oncology
JF - The lancet oncology
IS - 11
ER -