Heightened IDO1 levels predict Bacillus Calmette-Guèrin failure in high-risk non-muscle-invasive bladder cancer patients
Alice Turdo, Gabriele Tulone, Sebastiano Di Bella, Gaetana Porcelli, Caterina D’Accardo, Miriam Gaggianesi, Chiara Modica, Simone Di Franco, Francesca Angeloro, Giulia Bozzari, Vincenzo Davide Pantina, Melania Lo Iacono, Cristina Minasola, Rosa Giaimo, Annamaria Martorana, Nicola Pavan, Matilde Todaro, Alchiede Simonato, Giorgio Stassi
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.