Heightened IDO1 levels predict Bacillus Calmette-Guèrin failure in high-risk non-muscle-invasive bladder cancer patients
- Authors: Turdo, Alice; Tulone, Gabriele; Di Bella, Sebastiano; Porcelli, Gaetana; D'Accardo, Caterina; Gaggianesi, Miriam; Modica, Chiara; Di Franco, Simone; Angeloro, Francesca; Bozzari, Giulia; Pantina, Vincenzo Davide; Lo Iacono, Melania; Minasola, Cristina; Giaimo, Rosa; Martorana, Anna; Pavan, Nicola; Todaro, Matilde; Simonato, Alchiede; Stassi, Giorgio
- Publication year: 2025
- Type: Articolo in rivista
- OA Link: http://hdl.handle.net/10447/678345
Abstract
: Recent studies have indicated a potential link between immune-related gene expression and Bacillus Calmette-Guèrin (BCG) treatment response in non-muscle-invasive bladder cancer (NMIBC) patients, however, prognostic gene signatures have not significantly improved risk stratification beyond clinical characteristics. To identify predictive biomarkers in T1 high-risk (HR) bladder cancer (BC) patients responding to BCG treatment, a gene signature was derived from a discovery cohort of 73 BCG-naïve patients, both responders and non-responders, using the publicly available dataset GSE1542618. Among the identified genes, Indoleamine 2,3-dioxygenase (IDO1), an immunosuppressive enzyme, emerged as a crucial determinant of treatment outcomes. The association between IDO1 expression and worse prognosis was subsequently validated in a cohort of 75 BC patients using formalin-fixed paraffin-embedded (FFPE) BC specimens collected prior BCG treatment. This research revealed significant insights into the mechanisms underlying unsatisfactory responses to BCG treatment in HR patients, posing IDO1 as a promising prognostic biomarker and therapeutic target for NMIBC.