HMGB1, An Autophagy-Associated Gene, as a Novel Non-Invasive Diagnostic Biomarker: Clinicopathologic Correlation in Urinary Bladder Carcinoma Patients.

BACKGROUND

Urinary bladder cancer (UBC) is a leading cause of cancer-related morbidity and mortality worldwide, but current diagnostic methods are invasive and prone to false-negatives. This study aimed to evaluate the diagnostic and prognostic value of HMGB1 protein expression in urothelial carcinoma of the bladder using three distinct methods (serum ELISA, tissue IHC, and mRNA expression) via reverse transcription polymerase chain reaction (RT-PCR) and establishing their correlation.

METHODS

This single-center prospective observational study enrolled adults planned for transurethral resection of bladder tumor (TURBT) from March 2023 to April 2025 at Banaras Hindu University, India. The study enrolled 64 UBC patients and 21 control subject. For analysis, 5 ml of blood and cystoscopic guided tumor tissue were retrieved from UBC patients undergoing TURBT and normal bladder urothelium, and 5 mL blood was retrieved from noncancerous subjects (controls) undergoing cystoscopy for various reasons. Clinicopathologic features including tumor stage (T), grade, risk group, and imaging data also were analyzed with respect to their correlation with HMGB1 expression.

RESULTS

Levels of HMGB1 were significantly elevated in the UBC patients compared with the control patients (serum ELISA [p < 0.001], mRNA [p = 0.002], IHC [p = 0.013]). Expression of HMGB1 correlated significantly with tumor stage (T) and grade, with higher levels observed in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC). Notably, HMGB1 expression was highest in very-high-risk NMIBC patients. However, correlations with age, sex, MRI-VIRADS score, tumor size, and number of growths were statistically insignificant.

CONCLUSIONS

Elevated levels of HMGB1 correlated with advanced tumor stage, high grade, and MIBC, suggesting its utility in early detection and risk stratification, making it a non-invasive diagnostic and prognostic biomarker for UBC.