Abstract 7853: A seven-gene mutation signature predicts immunotherapy benefit in bladder cancer.

Abstract Introduction: Immunotherapy plays an important role in advanced bladder cancer. However, no mutation-based biomarker has been established to reliably predict immunotherapy benefit in bladder cancer. This study aimed to identify the gene mutation signature predicting immunotherapy efficacy. Method: We retrieved genetic and clinical data of patients with bladder cancer and immunotherapy treatment from MSK-TMB cohort. We selected targeted mutation genes if they occurred in more than three patients, with a higher incidence rate in survival patients, and belonged to non-synonymous mutation. Based on the selected genes, we categorized patients into three groups: compound mutation, single mutation and wild-type group. We compared the efficacy on overall survival (OS) among the three groups. Tumor mutation burden (TMB) was then integrated with the selected gene mutation information for further survival analysis. Result: A total of 215 patients from MSK-TMB cohort were included. The mean age was 67.1-year-old. The cohort consisted 116 (80.6%) males and the mean TMB was 11.7/megabase. Among 468 identified genes, seven genes were found following the selection criteria.The median OS was not reached, 19, and 11 months in compound mutation group, single group and wild-type group (p < 0.001 for compound mutation vs. wild-type group, 0.0063 for single mutation vs. wild-type group, respectively). After integrating TMB status, a survival advantage was observed among patients in the compound mutation with low TMB (compound-L) group. The median OS was NR, 13.5, and 9.0 months in the compound-L, single mutation with low TMB (single-L), and wild-type with low TMB (WT-L) groups (p = 0.055 for compound-L vs. single-L; p < 0.001 for compound-L vs. WT-L, respectively). Discussion: These findings provide evidence that the seven-gene mutation signature has potential as a predictive biomarker for the efficacy of immunotherapy in metastatic bladder cancer. Furter validation and functional studies are warranted. Citation Format: I-Cheng Huang, Chun-Nan Kuo, . A seven-gene mutation signature predicts immunotherapy benefit in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7853.