Blood-based microRNAs as diagnostic biomarkers to discriminate localized prostate cancer from benign prostatic hyperplasia and allow cancer-risk stratification.

Prostate cancer (PCa) is the second most diagnosed malignancy, and the leading cause of cancer-associated mortality among males. Prostate-specific antigen (PSA) has long been used for the detection of PCa. However, PSA levels increase in PCa and benign prostatic hyperplasia (BPH), and are associated with a poor disease outcome. Circulating microRNAs (miRNAs) have been determined to be highly stable in the circulation, and could be utilized as biomarkers to improve disease diagnosis and management. In the present study, the effectiveness of four PCa-associated miRNAs in the discrimination of PCa from BPH and the risk-stratification of PCa was assessed. The study included 100 participants: 35 patients with localized PCa, 35 patients with BPH and 30 healthy subjects. Patients with PCa were categorized based on their tumor stage (T), PSA level and Gleason score (GS) into low-(T 1/2, PSA <10 ng/ml or GS ≤7) and high-risk groups (T 3/4, PSA >20 ng/ml or GS ≥8). Reverse transcription-quantitative polymerase chain reaction was employed to assess the miRNA expression in peripheral blood samples. Significantly reduced expression of miR-15a, miR-126, miR-192 and miR-377 was observed in patients with PCa compared with patients with BPH and healthy subjects. In addition, the expression of the four miRNAs was lower in high-risk PCa patients than in low-risk PCa patients, with miR-126 being the most downregulated. The expression of the four miRNAs was also significantly and independently associated with PCa. Receiver operating characteristic curve analysis revealed a significant ability of the miRNAs to distinguish patients with PCa from those with BPH, patients with PCa from controls and low-risk PCa from high-risk PCa. These data suggested that expression of these miRNAs in the blood circulation may be promising, non-invasive biomarkers for the early detection of localized PCa, and for PCa risk stratification. Further validations of the clinical implementation of these results are warranted in a larger cohort.