Downregulation of urinary cell-free microRNA-214 as a diagnostic and prognostic biomarker in bladder cancer

Abstract

Background and objectives: We aimed to investigate potential of urinary cell-free microRNA-214 (miR-214) as a noninvasive biomarker for bladder cancer in this report.

Methods: We screened miR-214 expression in medium from 2 bladder cancer cell lines to determine whether it is secretory. Then we validated expression of cell-free miR-214 in urine samples from an independent set of 192 preoperative bladder cancer patients, 80 matching postoperative patients and 169 healthy controls.

Results: miR-214 was secreted from bladder cancer cell lines. Cell-free miR-214 levels were significantly attenuated in preoperative urine from bladder cancer patients, whereas its expression significantly increased in matched postoperative urine. Underexpressed extracellular miR-214 in urine was significantly associated with higher tumor stage, higher lymph node status, higher grade, age and history of non-muscle-invasive bladder cancer (NMIBC). Urinary cell-free miR-214 could forcefully differentiate bladder cancer (area under the curve; AUC = 0.838; 95% CI = 0.796-0.875) patients from healthy controls. Additionally, miR-214 in urine supernatant could serve as an independent prognostic predicator of recurrence-free survival (RFS) and overall survival (OS) for patients with muscle-invasive bladder cancer (MIBC).

Conclusions: Urinary cell-free miR-214 is a hopeful biomarker for tumor stratification, early diagnosis and prognostic assessment of bladder cancer.

Keywords: bladder cancer; cell-free miR-214; circulating miRNAs; non-invasive diagnosis; prognostic factor.