Identification of a Novel MicroRNA Panel Associated with Metastasis Following Radical Prostatectomy for Prostate Cancer.

Abstract

This is a case control study designed to identify one or more novel microRNA sequences associated with metastasis following radical prostatectomy for clinically localized prostate cancer. Samples were obtained from patients with clinical evidence of metastatic disease following surgery (cases) and patients who showed no evidence of metastasis or biochemical recurrence at least 5 years following surgery (controls) as identified from a single-center, institutional database. Cases and controls were matched for tumor grade and duration of follow-up. Whole miRNome analysis identified 2,792 expressed miRNAs in 19 patient pairs. The 497 miRNA sequences with reads per million over 10, were used for analysis, bootstrapping with backward selection identified a panel of 5-miRNA (miR-17-3p, miR-27a-3p, miR-200a-3p, miR-375, and miR-376b-3p) with a risk score strongly associated with metastasis (AUC=89.5%, 95%CI=79.5-99.5%). Methodologically, most studies use the magnitude of differential expression with or without clinical judgement for selection of predictors for inclusion in panels. In order to strengthen the predictive model, a selection strategy was employed, bootstrapping with automated backwards selection, which relied on the strength of association for inclusion. A genome-wide analysis of microRNA expression identified a panel of 5 miRNAs strongly associated with prostate cancer metastasis following radical prostatectomy.