Classification based on tumor phenotypes enables the novel molecular characterization of esophagogastric junction cancer.

IF 5.1 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastric Cancer Pub Date : 2025-09-26 DOI:10.1007/s10120-025-01665-z

Kyota Takahashi, Keiichi Hatakeyama, Masanori Terashima, Takeshi Nagashima, Kenichi Urakami, Keiichi Ohshima, Atsushi Ochiai, Tadakazu Shimoda, Yusuke Koseki, Kenichiro Furukawa, Keiichi Fujiya, Yutaka Tanizawa, Yasuhiro Tsubosa, Etsuro Bando, Yae Kanai, Yasuto Akiyama, Ken Yamaguchi

{"title":"Classification based on tumor phenotypes enables the novel molecular characterization of esophagogastric junction cancer.","authors":"Kyota Takahashi, Keiichi Hatakeyama, Masanori Terashima, Takeshi Nagashima, Kenichi Urakami, Keiichi Ohshima, Atsushi Ochiai, Tadakazu Shimoda, Yusuke Koseki, Kenichiro Furukawa, Keiichi Fujiya, Yutaka Tanizawa, Yasuhiro Tsubosa, Etsuro Bando, Yae Kanai, Yasuto Akiyama, Ken Yamaguchi","doi":"10.1007/s10120-025-01665-z","DOIUrl":null,"url":null,"abstract":"Background: The incidence of esophagogastric junction (EGJ) cancer is increasing worldwide. Siewert type II EGJ cancer encompasses intestinal and gastric phenotypes; however, the molecular profiles and clinicopathological features remain unclear.Methods: Overall, 922 patients who underwent surgical resection for EGJ or gastric cancer from 2014 to 2023 were analyzed. The tumors were classified into intestinal and gastric phenotypes using immunohistochemistry. Molecular profiling was conducted using whole-exome sequencing, and clinicopathological features, mutational patterns, immune responses, and survival outcomes were investigated.Results: The intestinal phenotype exhibited frequent TP53 mutations and high NOX1 expression. High NOX1 expression was correlated with increased CD4 + and CD20 + lymphocyte infiltration. The intestinal phenotype was associated with better relapse-free survival (RFS) than the gastric phenotype. Metastatic patterns varied, with peritoneal and lymph node metastases being more common in the gastric and intestinal phenotypes, respectively. High NOX1 expression was an independent prognostic factor for RFS.Conclusions: EGJ cancers with intestinal and gastric phenotypes demonstrate distinct molecular and immune profiles that influence prognosis. The intestinal phenotype, characterized by TP53 mutations, high NOX1 expression, increased immune cell infiltration, and better survival outcomes, may impact EGJ cancer prognosis and could guide future diagnostic and therapeutic approaches.","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":5.1000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gastric Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10120-025-01665-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: The incidence of esophagogastric junction (EGJ) cancer is increasing worldwide. Siewert type II EGJ cancer encompasses intestinal and gastric phenotypes; however, the molecular profiles and clinicopathological features remain unclear.

Methods: Overall, 922 patients who underwent surgical resection for EGJ or gastric cancer from 2014 to 2023 were analyzed. The tumors were classified into intestinal and gastric phenotypes using immunohistochemistry. Molecular profiling was conducted using whole-exome sequencing, and clinicopathological features, mutational patterns, immune responses, and survival outcomes were investigated.

Results: The intestinal phenotype exhibited frequent TP53 mutations and high NOX1 expression. High NOX1 expression was correlated with increased CD4 + and CD20 + lymphocyte infiltration. The intestinal phenotype was associated with better relapse-free survival (RFS) than the gastric phenotype. Metastatic patterns varied, with peritoneal and lymph node metastases being more common in the gastric and intestinal phenotypes, respectively. High NOX1 expression was an independent prognostic factor for RFS.

Conclusions: EGJ cancers with intestinal and gastric phenotypes demonstrate distinct molecular and immune profiles that influence prognosis. The intestinal phenotype, characterized by TP53 mutations, high NOX1 expression, increased immune cell infiltration, and better survival outcomes, may impact EGJ cancer prognosis and could guide future diagnostic and therapeutic approaches.

查看原文本刊更多论文

基于肿瘤表型的分类使食管胃结癌的新分子表征成为可能。

背景：食管胃交界癌（EGJ）的发病率在世界范围内呈上升趋势。siwert II型EGJ癌包括肠和胃表型；然而，其分子特征和临床病理特征尚不清楚。方法：对2014年至2023年922例因EGJ或胃癌手术切除的患者进行分析。免疫组织化学法将肿瘤分为肠型和胃型。使用全外显子组测序进行分子谱分析，并研究临床病理特征、突变模式、免疫反应和生存结果。结果：肠道表型表现为TP53频繁突变和NOX1高表达。NOX1高表达与CD4 +、CD20 +淋巴细胞浸润增加相关。与胃表型相比，肠道表型与更好的无复发生存（RFS）相关。转移模式各不相同，腹膜和淋巴结转移分别在胃和肠表型中更常见。NOX1高表达是RFS的独立预后因素。结论：具有肠和胃表型的EGJ癌表现出不同的影响预后的分子和免疫谱。肠道表型以TP53突变、NOX1高表达、免疫细胞浸润增加、生存结果较好为特征，可能影响EGJ癌的预后，并可指导未来的诊断和治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Gastric Cancer 医学-胃肠肝病学

CiteScore

14.70

自引率

2.70%

发文量

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.