The Potential Role of MicroRNAs as Biomarkers in Benign Prostatic Hyperplasia: A Systematic Review and Meta-analysis

Context: Benign prostate hyperplasia (BPH) is one of the most common urologic diseases. However, the molecular and cellular mechanisms involving the stromal and epithelial components of the prostate that lead to BPH remain unclear. Objective: To review and evaluate the evidence implicating microRNAs (miRNAs) in the pathogenesis of BPH. Evidence acquisition: A systematic search of the PubMed and Embase databases was performed using the terms “benign prostate hypertrophy and miRNA” or (“benign prostate hypertrophy and microRNAs” or “miRNA” or “miR”) on July 31, 2017. Evidence synthesis: Sixty-four miRNAs from 37 selected articles were ranked according to p values (p 0.05). To avoid false positive results, Benjamini-Hochberg correction of p values was performed. Application of the robust rank aggregation method identified miR-221 as significantly associated with BPH (p = 0.013). The effect size (ES) was calculated for studies with miR-221 data to generate an estimate of the overall ES and its confidence interval. The ES for miR-221 was measured by the standardized mean difference obtained by dividing the difference in the average gene expression between the PCa and BPH groups by a pooled estimate of standard deviation. The random effects model was used to calculate the pooled ES due to the presence of heterogeneity among studies. Publication bias of the seven included studies was assessed by the Funnel plot and Egger’s test and it was detected in the overall analysis of the seven studies (p < 0.01). After the trim and fill procedure, Egger’s test revealed no evidence of publication bias (p = 0.76) Conclusions: miR-221 has the potential to be used both as a biomarker and novel target in the early diagnosis and therapy of BPH. Technological advances should enable the synthesis of pre-RNA or anti-RNA molecules within carrier vehicles that can be safely delivered into patients. The development of such new pharmacologic therapies should be lastly investigated as possible therapy of one of the most common urologic diseases among elderly men. Patient summary: miR-221 has the potential to be used both as a biomarker and novel target in the early diagnosis and therapy of benign prostate hyperplasia. The development of new pharmacologic therapies enabling the synthesis of anti-miR-221 should be lastly investigated as a possible therapy of one of the most common urologic diseases among elderly men.