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


RESULTS
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).


CONCLUSIONS
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.


BACKGROUND
Source MDX.
Division of Solid Tumor Oncology, Department of Medicine, Dana-Farber Cancer Institute, Boston, MA, USA.
Robert W
RW
Ross
Matthew D
MD
Galsky
Howard I
HI
Scher
Jay
J
Magidson
Karl
K
Wassmann
Gwo-Shu Mary
GS
Lee
Leah
L
Katz
Sumit K
SK
Subudhi
Aseem
A
Anand
Martin
M
Fleisher
Philip W
PW
Kantoff
William K
WK
Oh
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002369:Castration; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy; D012313:RNA / Q000097:blood*; D012307:Risk Factors; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D012313:RNA