MicroRNAs in tumor samples and urinary extracellular vesicles as a putative diagnostic tool for muscle-invasive bladder cancer

Purpose The identification of biomarkers characterizing the invasive potential of bladder cancer could enhance the clinical management of individual patients and therefore improve prognosis. The aim of this study was to define a miRNA panel in tumor tissues as well as in urinary extracellular vesicles (EVs) for discriminating muscle-invasive bladder cancer (MIBC) from non-muscle-invasive bladder cancer (NMIBC). Methods miRNA expression was analyzed in 24 formalin-fixed, paraffin-embedded (FFPE) tumor samples by microarray analysis and was further validated by qRT-PCR in 56 FFPE tumor samples as well as in 37 urinary EV samples. Results Microarray analysis revealed 63 miRNAs that were significantly differentially expressed (P < 0.05) between tissues from MIBC and NMIBC tumors. Five selected miRNAs (miR-146b-5p, miR-155-5p, miR-138-5p, miR-144-5p, and miR-200a-3p) were validated by qRT-PCR. The expression of all except miR-144-5p was significantly associated with high tumor grade. In urinary EVs, a different expression was verified for miR-146b-5p (P = 0.004) and miR-155-5p (P = 0.036), which exhibited significantly higher expression in urinary EVs from patients with MIBC. Conclusions miRNAs are promising biomarkers for the identification of invasive bladder carcinomas. Tissue samples as well as urinary EVs may serve as sources for miRNA analysis. This method, in addition to histopathology, could provide a new diagnostic tool and facilitate individual therapeutic decisions to select patients for early cystectomy.