Background/Objectives: The aim of this study was to identify response prediction and prognostic biomarkers in muscle-invasive bladder cancer (MIBC) patients undergoing neoadjuvant chemotherapy (NAC). Methods: A retrospective multicentre study including 191 patients with MIBC who received NAC previous to radical cystectomy (RC) between 1996 and 2013. Gene expression patterns were analysed in 34 samples from transurethral resection of the bladder (TURB) using Illumina microarrays. The expression levels of 45 selected differentially expressed genes between responders and non-responders to NAC were validated by quantitative PCR in an independent cohort of 157 patients. Regression analysis was used to identify predictors of downstaging and relapse. A nomogram for predicting downstaging and relapse-including clinicopathological and gene expression variables-was developed. Results: The expression levels of 1352 transcripts differed between responders and non-responders to NAC. A nomogram based on the most predictive clinical variables (age, Tis (in situ), gender, history of NMIBC, and lymphadenopathy) and genes selected following the Akaike information criterion (AIC) (CBTB16, CHMP6, DDX54, CASP8, LOR, and PLEC) was then created. In addition, a three-gene expression prognostic model to predict tumour relapse was generated. This model was able to discriminate between two groups of patients with a significantly different probability of tumour relapse (HR: 2.11; CI: 1.16-3.83, p = 0.01). Conclusions: Our nomogram based on gene expression and clinical data is a useful tool to predict downstaging and tumour relapse after NAC in MIBC patients. Further validation is warranted.
Biomedicines. 2025 Mar 18*** epublish ***
Meritxell Pérez, Juan José Lozano, Mercedes Ingelmo-Torres, Montserrat Domenech, Caterina Fernández Ramón, J Alfred Witjes, Antoine G van der Heijden, Maria José Requena, Antonio Coy, Ricard Calderon, Begoña Mellado, Antonio Alcaraz, Antoni Vilaseca, Maria J Ribal
Department of Urology, Hospital Universitari Terrassa, 08221 Terrassa, Spain., Plataforma Bioinformatica, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Clínic de Barcelona, 08036 Barcelona, Spain., Department of Urology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain., Medical Oncology Department, Fundació Althaia, Xarxa Assintencial Universitària de Manresa, 08242 Manresa, Spain., Urology Department, Fundació Althaia, Xarxa Assintencial Universitària de Manresa, 08242 Manresa, Spain., Department of Urology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Department of Urology, Reina Sofía University Hospital, IMIBIC, Cordoba University, 14014 Córdoba, Spain., Fundación Instituto Valenciano de Oncologia (IVO), 46009 Valencia, Spain., Translational Genomics and Targeted Therapeutics in Solid Tumors, Medical Oncology Department, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clínic de Barcelona, 08036 Barcelona, Spain., Uro-Oncology Unit, Department of Urology, Hospital Clinic de Barcelona, 08036 Barcelona, Spain.