Profiling of circulating microRNAs for prostate cancer biomarker discovery

Prostate cancer (PC) is the most frequent cancer in men in the Western world. Currently, serum prostate-specific antigen levels and digital rectal examinations are used to indicate the need for diagnostic prostate biopsy, but lack in specificity and sensitivity. Thus, many men undergo unnecessary biopsy, and better and less invasive tools for PC detection are needed. Furthermore, whereas aggressive PC should be treated immediately to prevent dissemination, indolent PC often does not progress and overtreatment should be avoided. Currently, the best predictors of aggressiveness are Gleason score and T-stage of the primary PC. Better tools to assess PC aggressiveness could aid in treatment decisions. Recently, circulating miRNAs have been suggested as potential new biomarkers for PC with diagnostic and prognostic potential. Here, to identify new serum miRNA biomarker candidates for PC, we performed genome-wide miRNA profiling of serum samples from 13 benign prostatic hyperplasia (BPH) control patients and 31 PC patients. Furthermore, we carefully reviewed the literature on circulating miRNA biomarkers for PC. Our results confirmed the de-regulation of miR-141 and miR-375, two of the most well-documented candidate miRNA markers for PC. Moreover, we identified several new potential serum miRNA markers for PC and developed three novel and highly specific (100 %) miRNA candidate marker panels able to identify 84 % of all PC patients (miR-562/miR-210/miR-501-3p/miR-375/miR-551b), 80 % of patients with disseminated PC when compared to BPH patients (let-7a*/miR-210/miR-562/miR-616), and 75 % of disseminated PC patients when compared to localized PC patients (miR-375/miR-708/miR-1203/miR-200a), demonstrating high potential of serum miRNAs for diagnosing and staging of PC.