Prediction of response to neoadjuvant chemotherapy in patients with muscle-invasive urothelial bladder cancer: role of immune-related gene expression.

This prospective study aimed at investigating the role of immune-related gene expression (GATA3, METTL3, ERCC2, PD-L1 and IFN-γ) in the prediction of response to platinum-based neoadjuvant chemotherapy (NAC) in treatment of muscle-invasive bladder cancer (MIBC). A total of 112 patients received four cycles of systemic cisplatin-based NAC and then were subjected to radiological and histopathological evaluation through taking bladder biopsy before surgery. Quantitative real-time RT-PCR assessed GATA3, METTL3 and ERCC2 mRNA expression in tissue samples. Immunohistochemical (IHC) staining was done for GATA3, PD-L1 and IFN-γ in tissue samples. Out of the 112 patients, only 104 completed the proposed protocol of systemic NAC and were included in the final analysis. Out of 104 patients, 43 (41.4%) were responders and the remaining 61 patients (58.6%) were assigned as non-responders. GATA3 and IFN-γ expressions were significantly higher in tumor tissue of the responders compared to non-responders. METTL3 and ERCC2 expressions were significantly lower in tumor tissue of the responders compared to non-responders, whereas, PD-L1 staining showed no significant difference between both groups. Our study suggests that GATA3, METTL3, ERCC2, and IFN-γ could serve as predictive biomarkers for NAC response in MIBC patients. Higher GATA3 and IFN-γ along with lower METTL3 and ERCC2 levels are positively correlated with better response to NAC.