For muscle-invasive bladder cancer (MIBC), there are no tissue biomarkers in clinical use that identify patients sensitive or resistant to neoadjuvant chemotherapy. The present study investigates how molecular subtypes impact pathological response and survival in 149 patients receiving preoperative cisplatin-based chemotherapy. Tumor classification was performed by transcriptomic profiling and by a 13-marker immunostaining panel. Furthermore, we explored differential gene expression and chemotherapy response beyond molecular subtypes. Tumors with Genomically Unstable (GU) and Urothelial-like (Uro) subtypes had higher proportions of pathological response and superior survival outcomes as compared to the Basal-Squamous (Ba/Sq) subtype following neoadjuvant chemotherapy and radical cystectomy. Based on our findings, we suggest that urothelial cancer of the luminal-like GU- and Uro-subtypes are more responsive to cisplatin-based chemotherapy. We also found the gene coding for osteopontin (SPP1) to display a subtype-dependent effect on chemotherapy response, confirmed at the protein level by immunohistochemistry. Combined analyses of second-generation, subtype-specific biomarkers may be an additional way forward to develop a more precision-based treatment approach for neoadjuvant chemotherapy in MIBC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.