Gastric cancer (GC) persists as a leading cause of global cancer morbidity and mortality, with its pathogenesis intricately linked to epigenetic dysregulation. Emerging research specifies the novelty of these mechanisms-including DNA methylation, histone modifications, non-coding RNAs (ncRNAs), and RNA modifications-in GC initiation, progression, and therapeutic resistance. This review systematically examines key epigenetic mechanisms in GC, dissect the therapeutic implications as diagnostic biomarkers and therapeutic targets. Key insights include (1) aberrant methylation of tumor suppressor genes (e.g., CDH1, RUNX3): in early carcinogenesis; (2) histone lactylation and acetylation modulating immune evasion (3) ncRNAs (e.g., miR-21, HOTAIR); as promising biomarkers; and (4) m6A RNA modification in chemotherapy resistance. We further discuss translational applications of epigenetic biomarkers in liquid biopsies and targeted therapies (e.g., DNMT/HDAC inhibitors). Integrating multi-omics and epigenetic editing technologies may advance precision medicine in GC.
Zeng et al. (Wed,) studied this question.