Heightened IDO1 levels predict Bacillus Calmette-Guèrin failure in high-risk non-muscle-invasive bladder cancer patients
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.
Authors
- Vincenzo Davide Pantina (ORCID: https://orcid.org/0000-0003-1144-0434)
- Gabriele Tulone (ORCID: https://orcid.org/0000-0002-5797-3351)
- Alice Turdo (ORCID: https://orcid.org/0000-0002-6152-4903)
- Simone Di Franco (ORCID: https://orcid.org/0000-0002-6217-2161)
- Chiara Modica (ORCID: https://orcid.org/0000-0002-7000-5216)
- Melania Lo Iacono (ORCID: https://orcid.org/0000-0002-9292-327X)
- Miriam Gaggianesi (ORCID: https://orcid.org/0000-0002-7810-856X)
- Caterina D’Accardo (ORCID: https://orcid.org/0000-0003-1171-8678)
- Rosa Giaimo (ORCID: https://orcid.org/0000-0002-3884-2380)
- Cristina Minasola (ORCID: https://orcid.org/0000-0002-8522-4008)
- Matilde Todaro (ORCID: https://orcid.org/0000-0001-8686-8043)
- Annamaria Martorana (ORCID: https://orcid.org/0000-0002-9560-1882)
- Gaetana Porcelli (ORCID: https://orcid.org/0000-0002-7991-407X)
- Giorgio Stassi (ORCID: https://orcid.org/0000-0002-1016-9059)
- Nicola Pavan (ORCID: https://orcid.org/0000-0001-7355-7625)
- Sebastiano Di Bella (ORCID: https://orcid.org/0000-0001-7161-303X)
- Alchiede Simonato (ORCID: https://orcid.org/0000-0001-9513-4869)
- Francesca Angeloro
- Giulia Bozzari
Institutions
- Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone" di Palermo (IT)
- University of Palermo (IT)
Publication Details
- Journal
- Cell Death Discovery
- Published
- 2025-04-26
- DOI
- https://doi.org/10.1038/s41420-025-02489-7
- Citations
- 5
- Primary Topic
- Bladder and Urothelial Cancer Treatments
- Type
- article
- Field-Weighted Citation Impact
- 10.03