The utility of urine-circulating miRNAs for detection of prostate cancer

Abstract

Background:In this paper, the utility of urine-circulating microRNAs (miRNAs) as the potential biomarker of prostate cancer (PCa), the second most prevalent male cancer worldwide, was evaluated.Methods:Cancerous (N=56) and non-cancerous (N=16) prostate tissues were analysed on TaqMan Low Density Array, with the initial screening of 754 miRNAs in a subset of the samples. The abundance of selected miRNAs was analysed in urine specimens from two independent cohorts of patients with PCa (N=215 overall), benign prostatic hyperplasia (BPH; N=23), and asymptomatic controls (ASC; N=62) by means of quantitative reverse transcription PCR.Results:Over 100 miRNAs were found deregulated in PCa as compared with non-cancerous prostate tissue. After thorough validation, four miRNAs were selected for the analysis in urine specimens. The abundance of miR-148a and miR-375 in urine was identified as specific biomarkers of PCa in both cohorts. Combined analysis of urine-circulating miR-148a and miR-375 was highly sensitive and specific for PCa in both cohorts (AUC=0.79 and 0.84) and strongly improved the diagnostic power of the PSA test (AUC=0.85, cohort PCa1), including the grey diagnostic zone (AUC=0.90).Conclusions:Quantitative measurement of urine-circulating miR-148a and miR-375 can serve as the non-invasive tool for sensitive and specific detection of PCa.

Plasma microRNA signature is associated with risk stratification in prostate cancer patients

“…In our study, we detected the clearest discrimination between intermediate‐ and high‐risk Gleason scores and PSA values by the plasma levels of miR‐148a, suggesting its crucial role in PCa. The significant upregulation of miR‐148a in PCa patients detected in our analyses is in line with other studies . Previously, its correlation with biochemical recurrence of PCa was demonstrated, and importantly was independent of PSA values .…”

“…The reported association of miR‐148a with biochemical recurrence substantiates our finding showing its involvement in high‐risk PCa patients who are commonly at higher risk for developing biochemical recurrence. Besides, similar to our plasma analyses, circulating miR‐148a in the urine of PCa patients was shown to be also associated with PSA values . Thus, plasma miR‐148a may be a potential noninvasive tumor marker that may improve the risk stratification of PCa patients.…”

MicroRNAs in Cancer: Challenges and Opportunities in Early Detection, Disease Monitoring, and Therapeutic Agents

“…Recent work by Stuopelyte et al ., [50] showed that urine may also be an excellent source of tumor-derived circulating diagnostic miRNAs. Initially, this study screened the miRNA expression profiles of a cohort of prostate cancer tissue samples to select potential biomarkers.…”

“…The levels of 2 miRNAs (miR-148a & miR-375) were further evaluated in urine samples from prostate cancer patients and healthy controls. These 2 miRNAs had significant diagnostic potential in 2 independent cohorts and appeared to improve specificity compared to the PSA test [50]. In summary, it is clear that different groups, even studying the same disease, discover different miRNA signatures in their cohort of patients.…”

Resveratrol and pterostilbene as a microRNA‐mediated chemopreventive and therapeutic strategy in prostate cancer

“…Aberrant expression of specific miRNAs has been reported: miRNAs are implicated as oncogenes or as tumor suppressors and found to be either upregulated or downregulated, respectively . Moreover, the significance of circulating miRNAs as potential chemopreventive and prognostic/predictive biomarkers for clinical development in cancer and other diseases has been indicated …”