RAD51 是一种催化同源重组 (HR) 的关键重组酶，通常在多种癌症中过度表达。 DNA 损伤修复（DDR）对于维持基因组完整性非常重要，这可以进一步确定治疗反应。在此，我们试图探讨RAD51在指导肌层浸润性膀胱癌（MIBC）治疗中的临床价值。在这项回顾性研究中，总共纳入了 823 名 MIBC 患者。中山医院（ZSHS）队列（n=134）和癌症基因组图谱-膀胱癌（TCGA-BLCA）队列（n=391）被纳入化疗反应调查。 IMvigor210 队列 (n=298) 用于探讨 RAD51 状态对程序性细胞死亡配体 1 (PD-L1) 阻断的预测功效。此外，还研究了 RAD51 与基因组不稳定性和肿瘤免疫环境的关联。 RAD51 过度表达的患者比 RAD51 低的患者更有可能从铂类化疗和免疫治疗中受益。 TMBhighPD-L1highRAD51high 亚组从 PD-L1 阻断中获得最佳临床益处。以基因组不稳定为特征的 RAD51 高肿瘤与 MIBC 中激活的免疫治疗途径的高度炎症和免疫原性背景相关。 RAD51 可以作为 MIBC 患者对铂类化疗和 PD-L1 抑制剂治疗反应的预测指标。此外，它还可以提高 TMB 和 PD-L1 的预测功效。版权所有 © 2024 Wolters Kluwer Health, Inc. 保留所有权利。

RAD51, a key recombinase that catalyzes homologous recombination (HR), is commonly overexpressed in multiple cancers. It is curial for DNA damage repair (DDR) to maintain genomic integrity which could further determine the therapeutic response. Herein, we attempt to explore the clinical value of RAD51 in therapeutic guidance in muscle-invasive bladder cancer (MIBC). In this retrospective study, a total of 823 patients with MIBC were included. Zhongshan hospital (ZSHS) cohort (n=134) and The Cancer Genome Atlas-Bladder Cancer (TCGA-BLCA) cohort (n=391) were included for the investigation of chemotherapeutic response. The IMvigor210 cohort (n=298) was utilized to interrogate the predictive efficacy of RAD51 status to programmed cell death ligand-1 (PD-L1) blockade. In addition, the association of RAD51 with genomic instability and tumor immune contexture was investigated. Patients with RAD51 overexpression were more likely to benefit from both platinum-based chemotherapy and immunotherapy rather than RAD51-low patients. The TMBhighPD-L1highRAD51high subgroup possessed the best clinical benefits from PD-L1 blockade. RAD51-high tumors featured by genomic instability were correlated to highly inflamed and immunogenic contexture with activated immunotherapeutic pathway in MIBC. RAD51 could serve as a prognosticator for treatment response to platinum-based chemotherapy and PD-L1 inhibitor in MIBC patients. Besides, it could also improve the predictive efficacy of TMB and PD-L1.Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.