Detection of miRNAs in urine of prostate cancer patients

Abstract

Background and aim: Prostate cancer (PCa) is the second most prevalent oncologic disease among men worldwide. Expression of various transcripts, including miRNAs, is markedly deregulated in cancerous prostate tissue. This study aimed at identifying a PCa-specific expression profile of miRNAs for subsequent use in noninvasive diagnostics. Materials and methods: MiRNA expression was profiled in 13 PCa tissues using human miRNA microarrays. Highly expressed miRNAs were selected for the analysis in urine of patients with PCa (N = 143) and benign prostate hyperplasia (BPH; N = 23) by means of real time PCR, while miRNAs showing the expression differences in relation to clinical variables were further analyzed in 52 PCa and 12 noncancerous prostate tissues (NPT) on TaqMan Low Density Arrays (TLDA). Results: Analysis of miRNA expression in prostate tissue linked miR-95 to aggressive form of PCa. This miRNA was up-regulated in high grade (P = 0.041), the TMPRSS2-ERG fusion-positive tumors (P = 0.026), and in patients with subsequently developed biochemical recurrence (BCR; P = 0.054) after radical prostatectomy. MiRNAs highly expressed in PCa tissues were also detectable in urine from PCa patients. Moreover, the urinary levels of miR-21 had significant discriminatory power (P = 0.010) to separate PCa patients from BPH, while the combined analysis of urinary miR-19a and miR-19b was prognostic for BCR. In PCa, the diagnostic potential of urinary miRNA panel (miR-21, miR-19a, and miR-19b) was higher than that of the PSA test (AUC = 0.738 vs. AUC = 0.514). Conclusions: Measurement of urinary levels of PCa-specific miRNAs could assist in more specific detection of PCa and prediction of BCR.

Keywords

• Prostate cancer
• miRNA
• Urine
• miR-21
• miR-19