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DNA methylation biomarkers of prostate cancer: Confirmation of candidates and evidence urine is the most sensitive body fluid for non‐invasive detection
Author(s) -
Payne Shan R.,
Serth Jűrgen,
Schostak Martin,
Kamradt Jőrn,
Strauss Arne,
Thelen Paul,
Model Fabian,
Day J. Kevin,
Liebenberg Volker,
Morotti Andrew,
Yamamura Su,
Lograsso Joe,
Sledziewski Andrew,
Semjonow Axel
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20967
Subject(s) - dna methylation , prostate cancer , urine , body fluid , medicine , prostate , dna , cancer detection , methylation , cancer , pathology , oncology , biology , gene , genetics , gene expression
BACKGROUND A prostate cancer (PCa) biomarker with improved specificity relative to PSA is a public health priority. Hypermethylated DNA can be detected in body fluids from PCa patients and may be a useful biomarker, although clinical performance varies between studies. We investigated the performance of candidate PCa DNA methylation biomarkers identified through a genome‐wide search. METHODS Real‐time PCR was used to measure four DNA methylation biomarkers: GSTP1 and three previously unreported candidates associated with the genes RASSF2 , HIST1H4K , and TFAP2E in sodium bisulfite‐modified DNA. Matched plasma and urine collected prospectively from 142 patients referred for prostate biopsy and 50 young asymptomatic males were analyzed. RESULTS Analysis of all biomarkers in urine DNA significantly discriminated PCa from biopsy negative patients. The biomarkers discriminated PCa from biopsy negative patients with AUCs ranging from 0.64 for HIST1H4K (95% CI 0.55–0.72, P < 0.00001) to 0.69 for GSTP1 (95% CI 0.60–0.77, P < 0.00001). All biomarkers showed minimal correlation with PSA. Multivariate analysis did not yield a panel that significantly improved performance over that of single biomarkers. All biomarkers showed greater sensitivity for PCa in urine than in plasma DNA. CONCLUSIONS Analysis of the biomarkers in urine DNA significantly discriminated PCa from biopsy negative patients. The biomarkers provided information independent of PSA and may warrant inclusion in nomograms for predicting prostate biopsy outcome. The biomarkers' PCa sensitivity was greater for urine than plasma DNA. The biomarker performances in urine DNA should next be validated in formal training and test studies. Prostate 69:1257–1269, 2009. © 2009 Wiley‐Liss, Inc.