以 RAD51 表达为生物标记物预测铂类化疗和 PD-L1 阻断剂治疗肌肉浸润性膀胱癌的疗效

IF 3.2 4区 医学 Q3 IMMUNOLOGY
Journal of Immunotherapy Pub Date : 2025-01-01 Epub Date: 2024-05-27 DOI:10.1097/CJI.0000000000000525
Bingyu Li, Kaifeng Jin, Zhaopei Liu, Xiaohe Su, Ziyue Xu, Ge Liu, Jingtong Xu, Yuan Chang, Yiwei Wang, Yu Zhu, Le Xu, Zewei Wang, Hailong Liu, Weijuan Zhang
{"title":"以 RAD51 表达为生物标记物预测铂类化疗和 PD-L1 阻断剂治疗肌肉浸润性膀胱癌的疗效","authors":"Bingyu Li, Kaifeng Jin, Zhaopei Liu, Xiaohe Su, Ziyue Xu, Ge Liu, Jingtong Xu, Yuan Chang, Yiwei Wang, Yu Zhu, Le Xu, Zewei Wang, Hailong Liu, Weijuan Zhang","doi":"10.1097/CJI.0000000000000525","DOIUrl":null,"url":null,"abstract":"<p><p>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 TMB high PD-L1 high RAD51 high 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.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"18-26"},"PeriodicalIF":3.2000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"RAD51 Expression as a Biomarker to Predict Efficacy of Platinum-Based Chemotherapy and PD-L1 Blockade for Muscle-Invasive Bladder Cancer.\",\"authors\":\"Bingyu Li, Kaifeng Jin, Zhaopei Liu, Xiaohe Su, Ziyue Xu, Ge Liu, Jingtong Xu, Yuan Chang, Yiwei Wang, Yu Zhu, Le Xu, Zewei Wang, Hailong Liu, Weijuan Zhang\",\"doi\":\"10.1097/CJI.0000000000000525\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 TMB high PD-L1 high RAD51 high 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.</p>\",\"PeriodicalId\":15996,\"journal\":{\"name\":\"Journal of Immunotherapy\",\"volume\":\" \",\"pages\":\"18-26\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Immunotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/CJI.0000000000000525\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Immunotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/CJI.0000000000000525","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/27 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

RAD51是催化同源重组(HR)的一种关键重组酶,在多种癌症中普遍存在过表达现象。它是DNA损伤修复(DDR)维持基因组完整性的关键,可进一步决定治疗反应。在此,我们试图探讨 RAD51 在肌肉浸润性膀胱癌(MIBC)治疗指导中的临床价值。在这项回顾性研究中,共纳入了823例肌层浸润性膀胱癌患者。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)被纳入研究,以调查化疗反应。IMvigor210队列(n=298)用于研究RAD51状态对程序性细胞死亡配体-1(PD-L1)阻断的预测效果。此外,还研究了RAD51与基因组不稳定性和肿瘤免疫环境的关系。与RAD51低表达患者相比,RAD51高表达患者更有可能从铂类化疗和免疫疗法中获益。TMBhighPD-L1highRAD51high亚组从PD-L1阻断治疗中获得的临床疗效最好。以基因组不稳定性为特征的RAD51高肿瘤与MIBC的高度炎症和免疫原性环境以及激活的免疫治疗途径相关。RAD51可作为MIBC患者对铂类化疗和PD-L1抑制剂治疗反应的预后指标。此外,它还能提高TMB和PD-L1的预测效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
RAD51 Expression as a Biomarker to Predict Efficacy of Platinum-Based Chemotherapy and PD-L1 Blockade for Muscle-Invasive Bladder Cancer.

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 TMB high PD-L1 high RAD51 high 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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Immunotherapy
Journal of Immunotherapy 医学-免疫学
CiteScore
6.90
自引率
0.00%
发文量
79
审稿时长
6-12 weeks
期刊介绍: Journal of Immunotherapy features rapid publication of articles on immunomodulators, lymphokines, antibodies, cells, and cell products in cancer biology and therapy. Laboratory and preclinical studies, as well as investigative clinical reports, are presented. The journal emphasizes basic mechanisms and methods for the rapid transfer of technology from the laboratory to the clinic. JIT contains full-length articles, review articles, and short communications.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信