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This review systemically explains major histone modification types, emphasizing histone lactylation, its biochemical basis, crosstalk with other marks, and functional roles in metabolic reprogramming, proliferation, migration and immune escape. It further details how histone acetylation, methylation and related modifications contribute to GC biology, and analyzes the clinical value of lactylation for diagnosis, prognosis, biomarkers, therapeutic targets and drug-resistance 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, LILI WANG2 , LING WANG3 , ZEFEN LI3,4 , RUIYING YOU 1 , XUEPING MENG 1 , YAZHEN GAO 1 , LEYI ZHU5 , SHUFEI WEI3 and MEIREN LI3  \n1Clinical Medical College of Jiujiang University, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China; 2Department of Emergency Medical, Jiujiang Maternal and Child Health Hospital, Jiujiang, Jiangxi 332000, P.R. China; 3Department of Pathology, Jiujiang University Hospital, Jiujiang, Jiangxi 332000, P.R. China; 4Clinical Medical College of Gannan University, Ganzhou, Jiangxi 61341000, P.R. China; 5The Third School of Clinical Medicine, Zhejiang Chinese  \nMedical University, Hangzhou, Zhejiang 310000, P.R. China  \nReceived December 6, 2025; Accepted March 10, 2026  \nDOI: 10.3892/ijo.2026.5878  \nAbstract. Histone modification is an important mechanism of epigenetic regulation. New histone modifications play key roles in the regulation of gene expression and in the devel‑ opment and progression of various diseases. In addition to histone modifications, epigenetic regulation includes classic pathways such as DNA methylation, chromatin remodeling complexes and non‑coding RNAs, which interact with eachother and jointly shape the occurrence and development of gastric cancer (GC) . The present study systematically elabo‑ rated on the role of histone modification in GC and introduced several main types of histone modification, including acetyla‑ tion, methylation, citrullination, ubiquitination and lactylation, focusing on histone lactylation modification and exploring its biochemical basis, interaction with other modifications and functions such as metabolic reprogramming, cell proliferation, migration and immune escape, covering non‑tumor and other cancer fields. On this basis, the specific application of histone modification (acetylation, methylation and other modifica‑ tions) in GC is further explained and the effects of histone lactylation on metabolic reprogramming, proliferation, migra‑ tion and immune escape of GC are analyzed in detail. Finally, the clinical significance of histone lactylation modifications in the diagnosis and prognosis of GC, biomarkers, therapeutic targets and drug resistance mechanisms provides a reference for an in‑depth understanding of the role of histone modifica‑ tions, especially lactylation modifications, in the development of GC and clinical transformation applications.  \nCorrespondence to: Professor Shufei Wei or Professor Meiren Li, Department of Pathology, Jiujiang University Hospital, 57 Xunyangdong Road, Jiujiang, Jiangxi 332000, P.R. China  \nE‑[mail: weishufei0429@163.com](mail: weishufei0429@163.com)  \nE‑mail: [40028300@163.com](40028300@163.com)  \nKey words: histone modification, gastric cancer, histone lactylation, epigenetic regulation, gene expression regulation, metabolic reprogramming, biomarkers/therapeutic target  \nContents  \n1. Introduction  \n2. Histone modification  \n3. Application of histone modifications in gastric cancer  \n4. Function of histone lactylation in gastric cancer  \n5. Clinical significance of histone lactylation modifications  \n6. Outlook  \n1. Introduction  \nGastric cancer (GC) is one of the deadliest cancers worldwide. It is the fifth most common malignancy worldwide and fourth leading cause of cancer‑related deaths (1) . The incidence rate of GC in men is twice that in women and there has been a notable increase in the number of cases among individuals under 50 years of age. Despite advances in surgery, chemo‑ therapy and targeted therapy, the overall survival rate of patients with advanced GC remains \u003C40% . Therefore, it is imperative to thoroughly investigate its pathogenesis in order to develop novel diagnostic and therapeutic approaches (2) .  \nResearch suggests that aberrant epigenetic regulation is closely related to GC and plays a significant role in the course of this illness (3) . Post‑translational mo","cbCaibrNAw3k5C4C","https://ap.wps.com/l/cbCaibrNAw3k5C4C","pdf",1911186,14,"English","# Introduction\n# Histone modification\n# Application of histone modifications in gastric cancer\n# Function of histone lactylation in gastric cancer\n# Clinical significance of histone lactylation modifications\n# Outlook","[{\"question\":\"What is the main epigenetic role of histone modifications in gastric cancer?\",\"answer\":\"Histone modifications regulate gene transcriptional activity and influence GC initiation and progression by dynamically controlling chromatin and related pathways.\"},{\"question\":\"Which histone modification is emphasized in the review?\",\"answer\":\"The review focuses on histone lactylation, examining its biochemical basis, interactions with other modifications, and its downstream functions in GC.\"},{\"question\":\"How does histone lactylation relate to tumor behavior and clinical relevance?\",\"answer\":\"Histone lactylation is linked to metabolic reprogramming, cell proliferation, migration and immune escape, and it is discussed for its value in diagnosis, prognosis, biomarkers, therapeutic targeting and drug resistance mechanisms.\"}]","Role of Histone Modifications in Gastric Cancer - Review | PDF",1790118240,35]