Overexpression of miR-20a-5p in Tumor Epithelium Is an Independent Negative Prognostic Indicator in Prostate Cancer-A Multi-Institutional Study

Simple Summary MicroRNAs (miRs) have critical regulatory roles in cell functions, and are involved in prostate cancer tumorigenesis. miR-20a-5p is a member of the oncogenic miR-17-92 cluster. Overexpressed miR-20a-5p has been shown to increase both cell proliferation and cell migration in cancers. The aim of our cohort study was to evaluate the prognostic role of miR-20a-5p in prostate cancer. We found miR-20a-5p associated with biochemical failure in tumor epithelium and tumor stroma. In the multivariable analysis miR-20a-5p in tumor epithelium was found to be an independent prognostic predictor for biochemical failure. In the functional studies, migration and invasion were significantly increased in miR-20a-5p transfected prostate cancer cell lines. In conclusion, high miR-20a-5p expression in tumor epithelium is a negative independent prognostic factor for biochemical failure in prostate cancer. Objective: assessing the prognostic role of miR-20a-5p, in terms of clinical outcome, in a large multi-institutional cohort study. Methods: Tissue microarrays from 535 patients' prostatectomy specimens were constructed. In situ hybridization was performed to assess the expression level of miR-20a-5p in different tissue subregions: tumor stroma (TS) and tumor epithelium (TE). In vitro analysis was performed on prostate cancer cell lines. Results: A high miR-20a-5p expression was found negatively in association with biochemical failure in TE, TS and TE + TS (p = 0.001, p = 0.003 and p = 0.001, respectively). Multivariable analysis confirmed that high miR-20a-5p expression in TE independently predicts dismal prognosis for biochemical failure (HR = 1.56, 95% CI: 1.10-2.21, p = 0.014). Both DU145 and PC3 cells exhibited increased migration ability after transient overexpression of miR-20a-5p, as well as significant elevation of invasion in DU145 cells. Conclusion: A high miR-20a-5p expression in tumor epithelium is an independent negative predictor for biochemical prostate cancer recurrence.