GALNT14 drives gastric cancer aggressiveness via enzyme-dependent activation of a TGF-β-EMT-β-catenin axis in the post-Helicobacter pylori eradication era
- 1Liver Research Center, Linkou Chang Gung Memorial Hospital, 5F., No. 15, Wenhua 1st Rd., Guishan Dist., Taoyuan, 333423 Taiwan
- 2Department of Hepatology and Gastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan, 333423 Taiwan
- 3Division of Pediatric Gastroenterology, Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Linkou, Taoyuan 333423 Taiwan
Abstract
Background: Despite extensive effort to eradicate Helicobacter pylori (HP), gastric cancer (GC) remains a major global health burden. As HP-related carcinogenesis declines, host genetic factors are increasingly important for risk prediction and management in the post-HP eradication era. The GALNT14-rs9679162 polymorphism, previously linked to gastrointestinal malignancies, may influence GC susceptibility and outcomes, but its pathogenic role remains unclear.
Methods: A total of 472 subjects undergoing routine gastroscopy were analyzed, including 275 GC patients and 197 controls. Clinicopathological features, HP infection, and GALNT14-rs9679162 genotypes were assessed. Associations with GC risk and survival were evaluated by logistic and Cox regression. GALNT14 function was examined in tissues and immortalized gastric epithelial cells expressing wild-type or mutant GALNT14.
Results: This study was conducted in Taiwan, where anti-HP treatment was covered by national health insurance. As a result, GC patients were associated with lower concurrent HP infection (30.2% vs. 66.5%) (P < 0.001). The percentage of GALNT14-rs9679162 “GG” genotype was higher in GC (28.7% vs. 19.8%, P = 0.036) and independently associated with an increased risk (adjusted OR = 1.86, P = 0.040). Among GC patients, the “GG” genotype predicted higher recurrence (35.4% vs. 10.7%) and metastasis (44.3% vs. 24.5%) (both P < 0.01). Additionally, it was associated with poorer overall, recurrence-free, and metastasis-free survival (HR = 2.36–4.16, all P < 0.001). The “GG” genotype was associated with higher tissue expression of GALNT14 and its ectopic expression in immortalized gastric epithelial cells enhanced proliferative, migratory, anchorage-independent, and tumorigenic phenotypes via TGF-β/β-catenin–driven epithelial–mesenchymal transition.
Conclusion: GALNT14-rs9679162 “GG” serves as a prognostic marker and host genetic factor associated with aggressive gastric cancer in the post-HP eradication era, revealing a potential link between germline variation, GALNT14 upregulation, and aggressive gastric epithelial behavior.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12967-026-08725-7.
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BibTeX
@article{chen2026galnt14,
title = {{GALNT14 drives gastric cancer aggressiveness via enzyme-dependent activation of a TGF-β-EMT-β-catenin axis in the post-Helicobacter pylori eradication era}},
author = {Tsung-Hsing Chen and Sheng-Hsuan Lin and Yi-Ping Hsu and Wey-Ran Lin and Ming-Wei Lai and Yu-De Chu and Chau-Ting Yeh},
journal = {Journal of Translational Medicine},
year = {2026},
month = jul,
doi = {10.1186/s12967-026-08725-7},
url = {https://doi.org/10.1186/s12967-026-08725-7},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - GALNT14 drives gastric cancer aggressiveness via enzyme-dependent activation of a TGF-β-EMT-β-catenin axis in the post-Helicobacter pylori eradication era
AU - Tsung-Hsing Chen
AU - Sheng-Hsuan Lin
AU - Yi-Ping Hsu
AU - Wey-Ran Lin
AU - Ming-Wei Lai
AU - Yu-De Chu
AU - Chau-Ting Yeh
PY - 2026
DA - 2026/07/30
JO - Journal of Translational Medicine
DO - 10.1186/s12967-026-08725-7
UR - https://doi.org/10.1186/s12967-026-08725-7
AB - Background: Despite extensive effort to eradicate Helicobacter pylori (HP), gastric cancer (GC) remains a major global health burden. As HP-related carcinogenesis declines, host genetic factors are increasingly important for risk prediction and management in the post-HP eradication era. The GALNT14-rs9679162 polymorphism, previously linked to gastrointestinal malignancies, may influence GC susceptibility and outcomes, but its pathogenic role remains unclear. Methods: A total of 472 subjects undergoing routine gastroscopy were analyzed, including 275 GC patients and 197 controls. Clinicopathological features, HP infection, and GALNT14-rs9679162 genotypes were assessed. Associations with GC risk and survival were evaluated by logistic and Cox regression. GALNT14 function was examined in tissues and immortalized gastric epithelial cells expressing wild-type or mutant GALNT14. Results: This study was conducted in Taiwan, where anti-HP treatment was covered by national health insurance. As a result, GC patients were associated with lower concurrent HP infection (30.2% vs. 66.5%) (P < 0.001). The percentage of GALNT14-rs9679162 “GG” genotype was higher in GC (28.7% vs. 19.8%, P = 0.036) and independently associated with an increased risk (adjusted OR = 1.86, P = 0.040). Among GC patients, the “GG” genotype predicted higher recurrence (35.4% vs. 10.7%) and metastasis (44.3% vs. 24.5%) (both P < 0.01). Additionally, it was associated with poorer overall, recurrence-free, and metastasis-free survival (HR = 2.36–4.16, all P < 0.001). The “GG” genotype was associated with higher tissue expression of GALNT14 and its ectopic expression in immortalized gastric epithelial cells enhanced proliferative, migratory, anchorage-independent, and tumorigenic phenotypes via TGF-β/β-catenin–driven epithelial–mesenchymal transition. Conclusion: GALNT14-rs9679162 “GG” serves as a prognostic marker and host genetic factor associated with aggressive gastric cancer in the post-HP eradication era, revealing a potential link between germline variation, GALNT14 upregulation, and aggressive gastric epithelial behavior. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12967-026-08725-7.
SN - 1479-5876
ER -