RESEARCH ARTICLE Elevated Serum MicroRNA Levels Associate with Absence of High-Grade Prostate Cancer in a Retrospective Cohort

To reduce treatment of indolent prostate cancer (PCa), biomarkers are needed to improve identification of patients with a low-risk of having aggressive disease. Over-treatment of these patients occurs because of uncertainty in the aggressiveness of the entire tumor based on the biopsies, which do not accurately sample multifocal tumors. Circulating micro-RNAs (miRNAs) are stable serummarkers and differential miRNA levels occur in men with PCa. The goal of this study was to identify circulating miRNAs that were associated with ag-gressive or indolent PCa. We measured circulating miRNAs in 150 patients prior to surgery and compared the miRNA levels to the pathology of the entire radical prostatectomy speci-men. For this study we used an exceptionally well-characterized cohort of patients who had benign prostatic hyperplasia (BPH), low-grade or high-grade PCa. Low-grade was defined as patients with 100%Gleason grade 3 tumor as determined by step-wise sectioning. High-grade PCa patients had 30-90 % Gleason grade 4+5 in the tumor. BPH patients had at least two biopsies negative for PCa. Twenty one miRNAs were selected for analysis. The miR-NAs were quantified by RT-qPCR and analyzed by logistic regression. High levels of 1