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The study investigates how Helicobacter pylori infection alters epithelial programs and the role of CFAP73 in gastric cancer development.

April 6, 2026Discover Oncology0 citationsOpen Access

Helicobacter pylori–linked gene CFAP73 rewires epithelial programs and shapes the gastric cancer microenvironment

HLHaiwen LiAnhui Medical University RWRan WeiAnhui Medical University YLYuhan LiuAnhui Medical University

Key Points

The study investigates how Helicobacter pylori infection alters epithelial programs and the role of CFAP73 in gastric cancer development.
Identified trend-associated genes using the Jonckheere–Terpstra test
Conducted random-forest modeling and validated findings in multiple cohorts
Performed functional analyses and single-cell RNA sequencing
Used ligand-receptor modeling for biological role assessment
Applied spatial transcriptomics for microenvironment analysis
CFAP73 is downregulated during HP infection, correlating with poor survival and reduced response to cisplatin
Loss of CFAP73 is linked to increased proliferation and oncogenic signaling
CFAP73_high tumors show increased immune effector cells and decreased pro-tumorigenic fibroblast states
Spatial transcriptomics revealed spatial segregation of CFAP73_high epithelial regions from tumor-promoting areas

Abstract

Helicobacter pylori (HP) infection is the strongest environmental driver of gastric cancer, yet the epithelial programs that are progressively disrupted during infection and are associated with malignant transformation remain unclear. Trend-associated genes across HP-infection datasets (GSE60662, GSE60427) were identified using the Jonckheere–Terpstra test and intersected with survival-associated genes in TCGA-STAD. Random-forest modeling, multiple independent validation cohorts, functional analyses, single-cell RNA-seq (GSE249874), ligand–receptor inference, and spatial transcriptomics were integrated to define the biological role and microenvironmental impact of CFAP73. CFAP73 emerged as the top tumor-protective gene progressively downregulated during HP infection and strongly predictive of favorable survival and cisplatin benefit. CFAP73 expression marked a tumor-suppressive epithelial state characterized by reduced proliferation, EMT inhibition, and activation of p53 and apoptotic pathways. Single-cell analysis showed CFAP73 predominantly in non-malignant epithelial cells, with HP infection driving its loss. CFAP73 + epithelial cells displayed increased LCN2 expression and attenuated oncogenic signaling. Microenvironmentally, CFAP73ₕigh tumors were enriched for effector and Th17 T cells and showed reduced exhausted T cells, Tregs, and pro-tumorigenic CAF states (iCAF, apCAF). Ligand–receptor modeling revealed that CFAP73 + epithelial cells received weaker WNT, TGFβ, and PDGF signals from CAFs but stronger cytotoxic interactions from T cells. Spatial transcriptomics confirmed spatial segregation of CFAP73 + epithelial regions from proliferative, hypoxic, immune-checkpoint–active niches. CFAP73 is a previously unrecognized epithelial tumor suppressor suppressed early during HP infection. Loss of CFAP73 may contribute to epithelial malignant reprogramming and reshapes fibroblast and T-cell states toward an immunosuppressive, pro-tumor microenvironment. CFAP73 represents a promising biomarker linking HP-driven mucosal injury to gastric cancer initiation, progression, and therapeutic response.

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