Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) has been the standard care for muscle-invasive bladder cancer (MIBC) for two decades. One third of NAC-treated patients achieve pathologic complete response (pT0N0), a proxy for improved survival after RC. Predicting response already at transurethral resection of bladder tumor (TUR-BT) would enable selective use of NAC, minimizing exposure to ineffective therapy. We aimed to identify tumor mRNAs associated with response across multiple transcriptomic studies, prioritizing subsequent biomarkers for validation. Three NAC-treated cohort with tumor transcriptomic profiles were included. Differential mRNA-expression analysis and subtype classification according to the Lund Taxonomy were performed. Within each cohort and subtype, genes were ranked by differential expression, and integrated into a meta rank-score. Survival associations of top genes in the NAC-cohorts were used to select candidate biomarkers for protein validation. Proliferation/late cell-cycle gene predicted response in Urothelial-like subtype and cytotoxic T- and NK-cell-related genes predicted response in Basal/Squamous tumors. These findings were validated by immunostainings for CCNB1 and NKG7, respectively. This integrative framework suggests a complex picture in which two NAC-predictive signals identify responders in a subtype dependent manner. The framework can be updated as new datasets become available, providing dynamic exploration of NAC-predictive biomarkers in MIBC.
NPJ precision oncology. 2026 Jul 03*** epublish ***
Aymeric Zadoroznyj, Pontus Eriksson, Carina Bernardo, Lena Tran, Carl-Adam Mattsson, Thomas W Flaig, Roland Seiler, Catherine M Tangen, Peter C Black, Seth P Lerner, David J McConkey, Mattias Höglund, Fredrik Liedberg, Gottfrid Sjödahl
Department of Translational Medicine, Lund University, Malmö, Sweden. ., Division of Oncology, Department of clinical sciences, Lund University, Lund, Sweden., Department of Translational Medicine, Lund University, Malmö, Sweden., Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO, USA., Department for BioMedical Research, Urology Research Laboratory, University of Bern, Bern, Switzerland; Department of Urology, Hospital Center Biel, Spitalzentrum Biel, Biel, Switzerland., SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., University of British Columbia, Vancouver, BC, Canada., Scott Department of Urology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA., Department of Urology, University of Rochester Medical Center, Rochester, NY, USA.