Urinary Cell-Free miR-93-5p/miR-191-5p Display Utility as NIMBC Biomarkers

Urinary cell-free mirR-93-5p and miR-191-5p may have utility as non-invasive biomarkers for rapid molecular subtype identification among patients with bladder cancer, according to findings from a single-center exploratory study published in BMC Urology.

Specifically, miR-191-5p exhibited significant downregulation in all patients with urothelial carcinoma vs healthy controls, as much as a 24-fold decrease; the median values were 0.0397 (95% CI, 0.042-0.165) and 0.97 (95% CI, 1.096-2.086) in the respective groups (P <.001). Furthermore, the receiver operating characteristic (ROC) curve conferred an area under the curve (AUC) of 0.937 (95% CI, 0.882-0.992), a sensitivity of 95.3%, and a specificity of 91.8%. The positive likelihood ratio was 11.62.

Moreover, miR-191-5p was associated with a reduction in the luminal-like group vs healthy control of 28.37-fold; the median values were 0.034 (95% CI, 0.005-0.147) vs 0.970 (95% CI, 1.096-2.086), respectively (P <.001). Additionally, the ROC curve conferred an AUC of 0.967 (95% CI, 0.923-1.000), with a sensitivity of 95.3%, and a specificity of 96.4%. The positive likelihood ratio was 26.5.

Furthermore, investigators noted miR-191-5p upregulation was significantly higher among patients with T-upstaging (P = .03), N-upstaging (P = .02), and M-upstaging (P = .03) through a 1-year time frame. The respective increases were 1.73-fold, 3.58-fold, and 4.08-fold.

Regarding miR-93-5p, it was found at a 4.3-fold elevated rate in basal-like tumors vs healthy tissue, with median values of 4.15 (95% CI, –0.007 to 21.588) vs 0.970 (95% CI, 1.097-2.086), respectively (P <.001). Furthermore, it was expressed at a 4.5-fold increase in basal-like vs luminal-like tumors, with respective median values of 4.15 (95% CI, –0.007 to 21.588) vs 0.929 (95% CI, 0.845-1.499; P <.001).

In addition, a 3.4-fold elevation of miR-93-5p was observed among high-grade tumors, with a median value of 2.40 vs 0.71 in healthy tissue (P = .004). Moreover, it was observed at a rate 1.4-fold lower in low-grade tumors vs high-grade tumors (P = .003). Furthermore, miR-93-5p increased with tumor size (r = 0.41, P <.001), presence of necrosis at a rate of 3.4-fold (P <.001), and accompanying carcinoma in situ (CIS) at a rate of 2.6-fold (P = .02).

“In this exploratory, single-center study, urinary cell-free miR-93-5p and miR-191-5p showed potential as non-invasive biomarkers associated with basal-like and luminal-like molecular subtype characteristics of invasive urothelial carcinoma,” Sami Berk Özden, MD, a professor in the Department of Urology at Osmaniye State Hospital, wrote in the publication with study co-investigators. “miR-93-5p was associated with basal-like tumor features linked to aggressive behavior, whereas reduced miR-191-5p expression was associated with the presence of invasive urothelial carcinoma. miR-31-5p appears to play a complementary role, particularly in the context of carcinoma in situ. Although these findings suggest possible clinical applicability, external validation in larger, independent cohorts is required before routine clinical implementation.”

The prospective cohort study included patients 18 years and older with clinically or radiologically suspicion of bladder cancer scheduled for transurethral resection of bladder tumor (TURBT). Patients must have had histologically confirmed invasive urothelial carcinoma following initial TURBT, no prior urinary tract malignancy, no significant chronic urinary tract diseases, and fit to undergo general anesthesia.

Urine samples at 300 mL were collected from patients and were centrifuged at 300×g for 5 to minutes. Then, the supernatant was isolated and recentrifuged at 300×g for 5 minutes. Afterward, the supernatant was collected and total RNA was isolated.

Patients on the study in the investigational and control groups had a mean age of 68.14 years (range, 30-89) and 64.69 years (range, 31-80). A total of 87.8% vs 83.7% in the respective arms were male, and 57.1% of the investigational group had luminal-like tumors. Most patients in the investigational group had stage T1 disease (85.7%).

Reference

Özden SB, Kalaycı A, Gürses İ, et al. Clinical utility of cell-free urine miR-93-5p, miR-191-5p, miR-31-5p for invasive urothelial carcinoma detection and immune signature-based subtyping. BMC Urol. Published January 15, 2026. doi:10.1186/s12894-026-02047-y