Urinary cell‐free microRNA biomarker could discriminate bladder cancer from benign hematuria

The most common symptom of bladder cancer (BC) is hematuria. However, not all patients with hematuria are diagnosed with BC. Here, we explored a novel method to discriminate BC from hematuria under nonmalignant conditions by measuring differences in urinary cell‐free microRNA (miRNA) expression between patients with BC and those with hematuria. A multicenter study was performed using 543 urine samples obtained from the National Biobank of Korea, including 326 BC, 174 hematuria and 43 pyuria without cancer. The urinary miR‐6124 to miR‐4511 ratio was considerably higher in BC than in hematuria or pyuria, and enabled the discrimination of BC from patients with hematuria at a sensitivity of >90% (p < 0.001). Conclusively, the proposed noninvasive diagnostic tool based on the expression ratio of urinary cell‐free miR‐6124 to miR‐4511 can reduce unnecessary cystoscopies in patients with hematuria undergoing evaluation for BC, with a minimal loss in sensitivity for detecting cancer. What's new? Noninvasive urinary biomarkers are promising tools for distinguishing nonmalignant hematuria from hematuria associated with bladder cancer during primary patient evaluation. MicroRNAs (miRNAs), which function as oncogenes or tumor suppressors in cancer and are highly stable in body fluids, are emerging markers for this purpose. In the present study, the expression ratio between two urinary cell‐free miRNAs, miR‐6124 and miR‐4511, was found to be significantly higher in patients with bladder cancer than in those with hematuria or pyuria. The findings suggest that noninvasive assessment of miR‐6124/miR‐4511 expression ratio could help prevent unnecessary cystoscopy procedures when discriminating benign from malignant hematuria.