Purpose: MicroRNAs (miRNAs) are non-protein-encoding RNA regulators and implicated in numerous biological and developmental processes. Recently, it has been suggested that miRNAs may be potential cancer biomarkers as stable miRNAs have been detected in biological fluids such as serum, plasma, and urine. We examined whether the expression of urinary cell-free miRNAs is different in patients with prostate cancer (CaP) and controls with benign prostatic hyperplasia (BPH).

Materials and Methods: Total 750 urines, 150 serum and 269 prostate tissues from patients with CaP, BPH, and prostate biopsy were used in the study. Candidate urinary miRNAs were selected from miRNA array data of the training set and validated by real-time PCR in test set (test set-1 and test set-2) and biopsy set. The candidate reference miRNAs were validated in reference miRNA set. Correlations of the levels of candidate miRNAs between tissue, urine and serum were investigate in matched samples. Finally, candidate miRNAs were evaluated in BPH tissues, surrounding non-cancer tissues, and matched cancer tissues. Since there is no accepted reference miRNA, all samples were normalized to the total miRNA concentration in the urine.

Results: There were significant differences in the expression of five urinary miRNAs between BPH controls and CaP patients. In particular, urinary hsv1-miR-H18 and hsv2-miR-H9-5p levels were higher in CaP patients, and have comparable diagnostic values to serum prostate specific antigen (PSA). Moreover, hsv2-miR-H9-5p showed a better diagnostic performance than serum PSA for patients in the PSA gray zone and transrectal biopsy. There was a significant correlation between hsv1-miR-H18 and hsv2-miR-H9-5p in tissue and urine samples, and two miRNAs were highly expressed in cancer tissues and surrounding non-cancer tissues than BPH tissues.

Conclusion: urinary cell-free miRNAs may be useful for detecting CaP; in particular, virus-encoded hsv1-miR-H18 and hsv2-miR-H9-5p are potentially important urinary diagnostic markers for CaP.