Zeng SH, Wu YQ, Zhang WJ, Wang YT, Xu L, Guo SJ. DNA methylation in gastric precancerous lesions: Molecular mechanisms and clinical translation. World J Clin Oncol 2026; 17(5): 118073 [DOI: 10.5306/wjco.v17.i5.118073]
Corresponding Author of This Article
Shao-Ju Guo, Professor, Department of Spleen and Stomach Diseases, Shenzhen Hospital of Traditional Chinese Medicine, Fuhua Road, Shenzhen 518000, Guangdong Province, China. gsjgsjgsj2024@163.com
Research Domain of This Article
Integrative & Complementary Medicine
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Si-Hui Zeng, Wei-Jian Zhang, Yi-Tian Wang, Lin Xu, Shao-Ju Guo, Department of Spleen and Stomach Diseases, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen 518000, Guangdong Province, China
Yu-Qi Wu, Department of Spleen and Stomach Diseases, Nanjing Hospital of Chinese Medicine affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, Jiangsu Province, China
Author contributions: Zeng SH and Guo SJ designed the research study; Zeng SH, Wu YQ and Zhang WJ performed the literature search, screening, and data extraction; Wang YT and Xu L contributed to critical analysis and interpretation; Zeng SH, Wu YQ and Zhang WJ analyzed the data and wrote the manuscript; Guo SJ acquired the funding; all authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 82374348.
Conflict-of-interest statement: All authors declare that they have no conflicts of interest regarding this work.
Corresponding author: Shao-Ju Guo, Professor, Department of Spleen and Stomach Diseases, Shenzhen Hospital of Traditional Chinese Medicine, Fuhua Road, Shenzhen 518000, Guangdong Province, China. gsjgsjgsj2024@163.com
Received: December 23, 2025 Revised: February 12, 2026 Accepted: March 26, 2026 Published online: May 24, 2026 Processing time: 148 Days and 19 Hours
Abstract
DNA methylation constitutes a central epigenetic mechanism driving the initiation and progression of gastric precancerous lesions (GPL). This review synthesizes current evidence on the molecular basis of methylation dysregulation in GPL, establishing a mechanistic framework encompassing upstream drivers (Helicobacter pylori infection, Epstein-Barr virus, host aging, metabolic reprogramming) and downstream biological consequences (tumor suppressor gene silencing, Wnt/β-catenin activation, epithelial-mesenchymal transition, and microenvironment remodeling). Clinically, DNA methylation biomarkers detected in tissue, blood, stool, gastric juice, and emerging breath samples demonstrate substantial utility for early screening, risk stratification, prognostic prediction, and therapeutic response monitoring. Furthermore, targeted strategies modulating methylation-regulating enzymes and methylation-guided chemoprevention represent promising precision intervention paradigms. Despite challenges including epigenetic heterogeneity and translational barriers, integrating multi-omics technologies and developing multimodal liquid biopsy assays will propel the clinical implementation of methylation-based management for GPL.
Core Tip: DNA methylation is a pivotal epigenetic driver in gastric precarcinogenesis, orchestrating the stepwise progression from precancerous lesions to cancer. Clinically, methylation biomarkers enable non-invasive early detection, risk stratification, and prognostic assessment. Therapeutically, targeting methylation-regulating enzymes and implementing methylation-guided chemoprevention represent promising precision intervention strategies.
