A novel combined miRNA and methylation marker panel (miMe) for prediction of prostate cancer outcome after radical prostatectomy
Abstract
Improved prognostic biomarkers are needed to guide personalized prostate cancer (PC) treatment decisions. Due to the prominent molecular heterogeneity of PC, multimarker panels may be more robust. Here, 25 selected top-candidate miRNA and methylation markers for PC were profiled by qPCR in malignant radical prostatectomy (RP) tissue specimens from 198 PC patients (Cohort 1, training). Using GLMnet, we trained a novel multimarker model (miMe) comprising nine miRNAs and three methylation markers that predicted postoperative biochemical recurrence (BCR) independently of the established clinicopathological CAPRA-S nomogram in Cox multivariate regression analysis in Cohort 1 (HR [95% CI]: 1.53 [1.26–1.84], p < 0.001). This result was successfully validated in two independent RP cohorts (Cohort 2, n = 159: HR [95% CI]: 1.35 [1.06–1.73], p = 0.015. TCGA, n = 350: HR [95% CI]: 1.34 [1.01–1.77], p = 0.04). Notably, in CAPRA-S low-risk patients, a high miMe score was associated with >6 times higher risk of BCR, suggesting that miMe may help identify PC patients at high risk of progression despite favorable clinicopathological factors postsurgery. Finally, miMe was a significant predictor of cancer-specific survival (p = 0.019, log-rank test) in a merged analysis of 357 RP patients. In conclusion, we trained, tested and validated a novel 12-marker panel (miMe) that showed significant independent prognostic value in three RP cohorts. In the future, combining miMe score with existing clinical nomograms may improve PC risk stratification and thus help guide treatment decisions.
Abstract
What's new?
Although localized prostate cancer (PC) can be cured by radical prostatectomy (RP), both over- and under-treatment remain a major clinical problem as currently available routine prognostic tools cannot accurately distinguish aggressive from non-aggressive PCs at time of diagnosis. Here, the authors report a novel combined miRNA/methylation marker panel (miMe) for PC prognosis that was a significant independent predictor of post-operative PC outcome in three large RP cohorts. The results suggest that miMe may help guide personalized treatment decisions in the future, e.g. by identifying high-risk PC patients who might be candidates for intensified therapy.
