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Background <p>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.</p> Methods <p>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.</p> Results <p>The intestinal phenotype exhibited frequent <i>TP53</i> mutations and high <i>NOX1</i> expression. High <i>NOX1</i> 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 <i>NOX1</i> expression was an independent prognostic factor for RFS.</p> Conclusions <p>EGJ cancers with intestinal and gastric phenotypes demonstrate distinct molecular and immune profiles that influence prognosis. The intestinal phenotype, characterized by <i>TP53</i> mutations, high <i>NOX1</i> expression, increased immune cell infiltration, and better survival outcomes, may impact EGJ cancer prognosis and could guide future diagnostic and therapeutic approaches.</p>

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

  • 期刊论文

  • 发表日期：

    2025年9月26日

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  • 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

摘要

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.