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Background <p>Gastric cancer is among the deadliest cancers worldwide, and gastric intestinal metaplasia is a key precancerous phase. Understanding the molecular drivers of abnormal proliferation in intestinal metaplasia (IM) is vital for identifying biomarkers and therapeutic targets.</p> Materials and Methods <p>Using single-cell RNA sequencing, we characterized the cellular and molecular dynamics of gastric epithelial tissues across disease stages: control, chronic superficial gastritis, and IM.</p> Results <p>We identified nine cell types, predominantly epithelial cells, that exhibited increased proliferation with disease progression, suggesting their role in early gastric carcinogenesis. Notably, the regulatory gene <i>TFF3</i> was significantly upregulated in IM-associated goblet cells (log<sub>2</sub><i>FC</i>&#xa0;&gt;&#xa0;1.5, adjusted <i>p</i>-value &lt;&#xa0;0.001) and correlated strongly with disease advancement. Kyoto Encyclopedia of Genes and Genomes analysis revealed the role of the mitogen-activated protein kinase signaling pathway in early gastric cancer, and copy number variation analysis showed a rise in copy number variations, especially in epithelial cells within the chronic superficial gastritis and IM groups.</p> Conclusions <p>These findings suggest that <i>TFF3</i> may drive the early stages of gastric cancer, although the precise regulatory mechanisms involved remain to be fully elucidated. Additionally, this research may provide valuable insights into the mechanisms underlying other precancerous lesions and related malignancies.</p>

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Single-Cell Transcriptomics Reveals Key Factors in Gastric Intestinal Metaplasia

  • 期刊论文

  • 发表日期：

    2026年1月5日

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  • Yingxia Li,
  • Libin Jiang,
  • Mingxia Zhou,
  • Bo Xiao,
  • Yali Liu,
  • Zhichao Li,
  • Hongtao Wen

摘要

Background

Gastric cancer is among the deadliest cancers worldwide, and gastric intestinal metaplasia is a key precancerous phase. Understanding the molecular drivers of abnormal proliferation in intestinal metaplasia (IM) is vital for identifying biomarkers and therapeutic targets.

Materials and Methods

Using single-cell RNA sequencing, we characterized the cellular and molecular dynamics of gastric epithelial tissues across disease stages: control, chronic superficial gastritis, and IM.

Results

We identified nine cell types, predominantly epithelial cells, that exhibited increased proliferation with disease progression, suggesting their role in early gastric carcinogenesis. Notably, the regulatory gene TFF3 was significantly upregulated in IM-associated goblet cells (log2FC > 1.5, adjusted p-value < 0.001) and correlated strongly with disease advancement. Kyoto Encyclopedia of Genes and Genomes analysis revealed the role of the mitogen-activated protein kinase signaling pathway in early gastric cancer, and copy number variation analysis showed a rise in copy number variations, especially in epithelial cells within the chronic superficial gastritis and IM groups.

Conclusions

These findings suggest that TFF3 may drive the early stages of gastric cancer, although the precise regulatory mechanisms involved remain to be fully elucidated. Additionally, this research may provide valuable insights into the mechanisms underlying other precancerous lesions and related malignancies.