Molecular features and prognostic factors of locally advanced microsatellite instability-high gastric cancer.

IF 6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Gastric Cancer Pub Date : 2024-07-01 Epub Date: 2024-05-14 DOI:10.1007/s10120-024-01506-5
Kenichiro Furukawa, Keiichi Hatakeyama, Masanori Terashima, Kenichi Urakami, Yusuke Koseki, Keiichi Fujiya, Yutaka Tanizawa, Etsuro Bando, Ken Yamaguchi
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Abstract

Background: Microsatellite instability-high (MSI-H) tumors are distinct molecular subtypes in gastric cancer. However, a few studies have comprehensively reported the molecular features of MSI-H tumors and their prognostic factors in locally advanced gastric cancer. This study aimed to clarify the molecular features and prognostic factors of locally advanced MSI-H gastric cancer.

Methods: This study included 499 patients with locally advanced gastric cancer who underwent radical gastrectomy. We evaluated the MSI status and compared with previously published whole-exome sequencing, panel sequencing, and gene expression profiling data. Clinicopathological characteristics and molecular profiles were compared between patients with MSI-H and microsatellite stable (MSS) gastric cancer. A subgroup analysis of survival was performed in patients with MSI-H gastric cancer.

Results: MSI-H tumors were detected in 79 of 499 patients (15.8%). MSI-H tumors were associated with an increased tumor mutational burden, MLH1 downregulation, CD274 (PD-L1) upregulation, and enrichment of cell cycle pathways. Among patients with MSI-H gastric cancer, the disease-specific survival (DSS) tended to be better in the surgery plus tegafur, gimeracil, and oteracil potassium (S-1) adjuvant chemotherapy group than in the surgery alone group, especially for stage III patients. Furthermore, DSS was better in the T cell-inflamed gene expression signature-high group, and it tended to be worse in the non-solid type poorly differentiated adenocarcinoma group.

Conclusions: The molecular features and prognostic factors of locally advanced MSI-H gastric cancer were clarified. S-1 adjuvant chemotherapy appears to be beneficial, and the T cell-inflamed gene expression signature and histopathological type are prognostic factors in MSI-H tumors.

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局部晚期微卫星不稳定性高胃癌的分子特征和预后因素
背景:微卫星不稳定性高(MSI-H)肿瘤是胃癌中独特的分子亚型。然而,只有少数研究全面报道了局部晚期胃癌中MSI-H肿瘤的分子特征及其预后因素。本研究旨在明确局部晚期MSI-H型胃癌的分子特征和预后因素:本研究纳入了499例接受根治性胃切除术的局部晚期胃癌患者。我们评估了患者的 MSI 状态,并与之前发表的全外显子组测序、面板测序和基因表达谱数据进行了比较。我们比较了MSI-H和微卫星稳定(MSS)胃癌患者的临床病理特征和分子图谱。对MSI-H胃癌患者的生存率进行了亚组分析:499例患者中有79例(15.8%)发现了MSI-H肿瘤。MSI-H肿瘤与肿瘤突变负荷增加、MLH1下调、CD274(PD-L1)上调和细胞周期通路丰富有关。在MSI-H型胃癌患者中,手术加替加氟、吉莫斯特和奥特拉西尔钾(S-1)辅助化疗组的疾病特异性生存率(DSS)往往优于单纯手术组,尤其是III期患者。此外,T细胞炎症基因表达特征高组的DSS较好,而非实体型分化不良腺癌组的DSS往往较差:结论:明确了局部晚期MSI-H型胃癌的分子特征和预后因素。结论:阐明了局部晚期MSI-H型胃癌的分子特征和预后因素,S-1辅助化疗似乎是有益的,T细胞炎症基因表达特征和组织病理学类型是MSI-H型肿瘤的预后因素。
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来源期刊
Gastric Cancer
Gastric Cancer 医学-胃肠肝病学
CiteScore
14.70
自引率
2.70%
发文量
80
审稿时长
6-12 weeks
期刊介绍: Gastric Cancer is an esteemed global forum that focuses on various aspects of gastric cancer research, treatment, and biology worldwide. The journal promotes a diverse range of content, including original articles, case reports, short communications, and technical notes. It also welcomes Letters to the Editor discussing published articles or sharing viewpoints on gastric cancer topics. Review articles are predominantly sought after by the Editor, ensuring comprehensive coverage of the field. With a dedicated and knowledgeable editorial team, the journal is committed to providing exceptional support and ensuring high levels of author satisfaction. In fact, over 90% of published authors have expressed their intent to publish again in our esteemed journal.
期刊最新文献
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