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REVIEW

The Double-Edged Sword of Genomic DNA Methylation: Orchestrating Gastric Carcinogenesis and Shaping Precision Oncology

Xuan Chen, Chao Luo, Wei Wen*
Department of Gastroenterology, Jiangsu Second Traditional Chinese Medicine Hospital, Nanjing, China
* Corresponding Author: Wei Wen. Email: email

Oncology Research https://doi.org/10.32604/or.2026.079753

Received 27 January 2026; Accepted 03 May 2026; Published online 15 June 2026

Abstract

This article systematically elaborates on the dual role of DNA methylation in the initiation and progression of gastric cancer and its potential clinical applications in precision oncology. As a core epigenetic mechanism, DNA methylation drives the multistage development of gastric cancer through the coordinated dysregulation of genome-wide hypomethylation and promoter-specific hypermethylation, playing a key role in chronic inflammation and epigenetic reprogramming, particularly in the context of Helicobacter pylori infection. The article focuses on analyzing the central pathogenic mechanisms of DNA methylation, including the silencing of tumor suppressor genes, induction of genomic instability, promotion of the CpG island methylator phenotype, and facilitation of epithelial-mesenchymal transition. It further explores the clinical utility of DNA methylation as a biomarker for early diagnosis, prognosis evaluation, recurrence monitoring, and prediction of therapeutic response in gastric cancer. Moreover, the article reviews epigenetic therapeutic strategies represented by hypomethylating agents and their potential and challenges when combined with chemotherapy or immunotherapy, envisioning an integrated precision medicine model based on methylation profiling.

Keywords

DNA methylation; gastric cancer; epigenetics; precision oncology; biomarker; liquid biopsy; hypomethylating agents; immunotherapy

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