MicroRNAs as biomarkers for prostate cancer prognosis: a systematic review and a systematic reanalysis of public data

Abstract

Background Reliable prognostic biomarkers to distinguish indolent from aggressive prostate cancer (PCa) are lacking. Many studies investigated microRNAs (miRs) as PCa prognostic biomarkers, often reporting inconsistent findings. We present a systematic review of these; also systematic reanalysis of public miR-profile datasets to identify tissue-derived miRs prognostic of biochemical recurrence (BCR) in patients undergoing radical prostatectomy. Methods Independent PubMed searches were performed for relevant articles from January 2007 to December 2019. For the review, 128 studies were included. Pooled-hazard-ratios (HRs) for miRs in multiple studies were calculated using a random-effects model (REM). For the reanalysis, five studies were included and Cox proportional-hazard models, testing miR association with BCR, performed for miRs profiled in all. Results Systematic review identified 120 miRs as prognostic. Five (let-7b-5p, miR-145-5p, miR152-3p, miR-195-5p, miR-224-5p) were consistently associated with progression in multiple cohorts/studies. In the reanalysis, ten (let-7a-5p, miR-148a-3p, miR-203a-3p, miR-26b-5p, miR30a-3p, miR-30c-5p, miR-30e-3p, miR-374a-5p, miR-425-3p, miR-582-5p) were significantly prognostic of BCR. Of these, miR-148a-3p (HR = 0.80/95% CI = 0.68-0.94) and miR-582-5p (HR = 0.73/95% CI = 0.61-0.87) were also reported in prior publication(s) in the review. Conclusions Fifteen miRs were consistently associated with disease progression in multiple publications or datasets. Further research into their biological roles is warranted to support investigations into their performance as prognostic PCa biomarkers.

Expression of miR-24-1-5p in Tumor Tissue Influences Prostate Cancer Recurrence: The PROCA-life Study

“…The histopathologic tumor stage was pT2c for 47.9% of the patients, while 26.1% had pT3, and the ISUP grade group was 1 or 2 for 73.8% of the patients. The median CAPRA-S score was 3 (39.4% Capra-S low (0-2), 46.5% Capra-S intermediate (3)(4)(5), and 14.1% Capra-S high (6)(7)(8)(9)(10)(11)(12). Positive surgical margins were found in 30.5% of the cases.…”

“…MicroRNAs (miRNAs) are a class of endogenous non-coding small RNA molecules associated with the regulation of gene expression and are “fine-tuners” of the immune system [ 3 ]. These have been studied for their potential to serve as molecular prognostic biomarkers for cancer including PCa [ 4 ]. In particular, differential miRNAs’ expression profiles between tumour and normal tissues have been observed for PCa, as well as for other other cancer types [ 4 , 5 ].…”

“…These have been studied for their potential to serve as molecular prognostic biomarkers for cancer including PCa [ 4 ]. In particular, differential miRNAs’ expression profiles between tumour and normal tissues have been observed for PCa, as well as for other other cancer types [ 4 , 5 ]. In a recent systematic review, fifteen miRNAs were associated with PCa prognosis [ 4 ].…”

“…In particular, differential miRNAs’ expression profiles between tumour and normal tissues have been observed for PCa, as well as for other other cancer types [ 4 , 5 ]. In a recent systematic review, fifteen miRNAs were associated with PCa prognosis [ 4 ]. These are transcribed as ~70 nucleotide precursors in a stem-loop sequence and are subsequently processed by the Dicer enzyme to give two mature ~22 nucleotide products.…”

“…The effects of miRNAs in prostate cancer have been studied, but the biological mechanisms operating, as well as the types of miRNAs and their functions, have not yet been clarified [ 4 , 6 , 21 , 22 ]. Importantly, no prostate-specific miRNAs have yet been definitively identified.…”