TY  - EJOU
AU  - Ricciardi, Gabriele 
AU  - Ballato, Mariagiovanna 
AU  - Tralongo, Pietro 
AU  - Rossanese, Marta 
AU  - Pepe, Ludovica 
AU  - Ieni, Antonio 
AU  - Fadda, Guido 
AU  - Ficarra, Vincenzo 
AU  - Fiorentino, Vincenzo 
AU  - Pierconti, Francesco 
AU  - Martini, Maurizio 

TI  - The AR-ADAR2-PD-L1 Axis as a Prognostic Biomarker System in BCG-Treated High-Grade Papillary Urothelial Carcinoma: A Single-Center Retrospective Cohort Study
T2  - Oncology Research

PY  - 
VL  - 
IS  - 
SN  - 1555-3906

AB  - <b>Background:</b> High-grade papillary urothelial carcinoma (HG-PUC) represents a high-risk non-muscle-invasive bladder cancer with frequent recurrence after intravesical Bacillus Calmette-Guérin (BCG) therapy, and reliable prognostic biomarkers remain lacking. The aim of this study was to evaluate the prognostic significance of the androgen receptor (AR)-ADAR2-programmed death-ligand 1 (PD-L1) axis in BCG-treated HG-PUC. <b>Methods:</b> A single-center retrospective cohort of 146 patients with HG-PUC treated with transurethral resection followed by intravesical BCG was evaluated. AR, ADAR2, PD-L1, CD4, and CD8 expression were evaluated by immunohistochemistry. miR-200a-3p and interferon-γ (IFN-γ) transcript expression were assessed by quantitative PCR in an exploratory subgroup of 40 patients. Associations between molecular markers, clinicopathological variables, and Recurrence-Free Survival were assessed. <b>Results:</b> High AR expression was significantly associated with reduced ADAR2 expression, increased PD-L1 expression, higher CD4/CD8 ratios, and shorter RFS (all <i>p</i> &lt; 0.0001). AR, ADAR2, and PD-L1 remained independent prognostic factors for RFS in multivariable analysis, and their combined model showed good prognostic discrimination (Harrell’s C-index = 0.792, 95% CI 0.754–0.830). During a median follow-up of 10 months (95% CI, 9–12), 52 RFS events occurred. In the exploratory cohort, tumors with low AR and high ADAR2 expression exhibited significantly higher miR-200a-3p and IFN-γ transcript levels. <b>Conclusions:</b> The AR-ADAR2-PD-L1 molecular profile was independently associated with RFS in patients with BCG-treated HG-PUC. These findings support its potential role in prognostic risk stratification, although prospective external validation and functional studies are required before clinical implementation.
KW  - Androgen receptor; ADAR2; high-grade papillary urothelial carcinoma; BCG treatment; non-muscle-invasive bladder cancer; miR-200a-3p; PD-L1

DO  - 10.32604/or.2026.086237