Comparative Evaluation of HMG Family Proteins and miR-106a-5p in Low-Grade Non-Invasive and High-Grade Muscle-Invasive Papillary Urothelial Carcinoma

Urothelial carcinoma (UC) of the bladder exhibits low- and high-grade papillary forms with distinct prognoses. High mobility group proteins (HMGA1, HMGA2, HMGB1) and miR-106a-5p are involved in tumor progression, but their interplay in UC remains incompletely understood. The aim of this study was to compare the expression of these parameters in low- and high-grade papillary UC. Tissue samples from 80 patients (40 low-grade and 40 high-grade) undergoing transurethral resection or cystectomy were analyzed, with control samples consisting of tumor-adjacent tissues without histopathological alterations obtained from the same patients. HMGA1, HMGA2, and HMGB1 protein expression was assessed immunohistochemically. Gene expression was quantified by real-time PCR, and miR-106a-5p levels were measured by droplet digital PCR. Statistical analysis was conducted using Statistica 13.3, applying one-way ANOVA with Tukey’s post hoc test and correlation analysis, with p < 0.05 considered significant. Expression of HMGA1 and HMGB1 was reduced in low-grade papillary urothelial carcinoma compared to control tissues, whereas both proteins were significantly increased in high-grade lesions. HMGA2 expression was minimal in low-grade tumors but partially restored in high-grade tumors. Analysis revealed the highest levels of miR-106a-5p in normal urothelium, slightly decreased in low-grade tumors, and significantly reduced in high-grade cancers. HMG proteins and miR-106a-5p demonstrate distinct expression patterns in low- versus high-grade papillary UC, which correlates with tumor aggressiveness. These molecules may serve as diagnostic and prognostic biomarkers. Their potential as therapeutic targets requires further mechanistic and translational investigation.