A five-CpG DNA methylation score to predict metastatic-lethal outcomes in men treated with radical prostatectomy for localized prostate cancer.

摘要: BACKGROUND Prognostic biomarkers for localized prostate cancer (PCa) could improve personalized medicine. Our group previously identified a panel of differentially methylated CpGs in primary tumor tissue that predict disease aggressiveness, and here we further validate these biomarkers. METHODS Pyrosequencing was used to assess CpG methylation eight using the HumanMethylation450 array; with strongly correlated (r >0.70) results were considered technically validated. Logistic regression incorporating validated Gleason sum define lock final model stratify men metastatic-lethal versus non-recurrent PCa training dataset. Coefficients from then construct DNA score, which evaluated by logistic Receiver Operating Characteristic (ROC) curve analyses an independent testing RESULTS Five all retained (P < 0.05) model. The 5-CpG coefficients calculate higher progression (P = 6.8 × 10-6 ) For each unit increase score there four-fold risk events (odds ratio, OR = 4.0, 95%CI = 1.8-14.3). At 95% specificity, sensitivity 74% compared 53% alone. demonstrated better prediction performance (AUC = 0.91; pAUC = 0.037) alone (AUC = 0.87; pAUC = 0.025). CONCLUSIONS improved upon predicting holds promise stratification aggressive tumors. This prognostic warrants evaluation as tool improving patient outcomes.