Distinct age-related effects of homologous recombination deficiency on genomic profiling and treatment efficacy in gastric cancer.

IF 6.9 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Journal of Gastroenterology Pub Date : 2025-06-13 DOI:10.1007/s00535-025-02267-3

Yoshie Maki, Yoshiyasu Kono, Toshiki Ozato, Hideki Yamamoto, Akira Hirasawa, Daisuke Ennishi, Shuta Tomida, Shinichi Toyooka, Kenta Hamada, Masaya Iwamuro, Seiji Kawano, Motoyuki Otsuka

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引用次数: 0

Abstract

Background: The incidence of gastric cancer among younger patients is increasing globally, with growing attention being paid to the role of homologous recombination deficiency (HRD). However, the effect of HRD on treatment outcomes and prognosis in this population remains unclear.

Methods: We analyzed clinical and genomic data from the Center for Cancer Genomics and Advanced Therapeutics database. Younger patients (≤ 39 years, n = 140) were compared with older patients (≥ 65 years, n = 1118) diagnosed with gastric cancer. This study focused on mutations in homologous recombination repair (HRR) genes and their association with tumor mutation burden (TMB), microsatellite instability (MSI), and treatment outcomes.

Results: In older patients, HRD was associated with higher TMB and microsatellite instability-high (MSI-H) status, whereas no such correlations were observed in younger patients. Notably, MSI-H status was not observed in the younger group. Younger patients with HRD had a significantly shorter time to treatment failure (TTF) and overall survival (OS) than those without HRD. Conversely, in older patients, there was no significant difference in TTF or OS based on HRD status.

Conclusion: HRR gene mutations influence genomic profiling, TMB, and MSI differently depending on the age of gastric cancer onset, suggesting potential effects on treatment efficacy and prognosis.

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同源重组缺乏对胃癌基因组谱和治疗效果的明显年龄相关性影响。

背景：随着同源重组缺陷（homologous recombination deficiency， HRD）的作用越来越受到人们的关注，胃癌在全球年轻患者中的发病率正在上升。然而，HRD对该人群的治疗结果和预后的影响尚不清楚。方法：我们分析了来自癌症基因组学和高级治疗中心数据库的临床和基因组数据。年轻患者（≤39岁，n = 140）与老年胃癌患者（≥65岁，n = 1118）进行比较。本研究的重点是同源重组修复（HRR）基因突变及其与肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）和治疗结果的关系。结果：在老年患者中，HRD与较高的TMB和微卫星不稳定-高（MSI-H）状态相关，而在年轻患者中没有观察到这种相关性。值得注意的是，年轻组中未观察到MSI-H状态。年轻HRD患者的治疗失败时间（TTF）和总生存期（OS）明显短于无HRD患者。相反，在老年患者中，基于HRD状态的TTF或OS没有显著差异。结论：HRR基因突变对基因组谱、TMB和MSI的影响随胃癌发病年龄的不同而不同，可能影响治疗效果和预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gastroenterology 医学-胃肠肝病学

CiteScore

12.20

自引率

1.60%

发文量

审稿时长

4-8 weeks

期刊介绍： The Journal of Gastroenterology, which is the official publication of the Japanese Society of Gastroenterology, publishes Original Articles (Alimentary Tract/Liver, Pancreas, and Biliary Tract), Review Articles, Letters to the Editors and other articles on all aspects of the field of gastroenterology. Significant contributions relating to basic research, theory, and practice are welcomed. These publications are designed to disseminate knowledge in this field to a worldwide audience, and accordingly, its editorial board has an international membership.