Huang HY, Lan J, Zhuang W. Role of circulating tumor DNA methylation in gastric cancer initiation and progression: A comprehensive review. World J Gastrointest Oncol 2025; 17(8): 107412 [DOI: 10.4251/wjgo.v17.i8.107412]
Corresponding Author of This Article
Wei Zhuang, MD, Department of Intensive Care Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No. 1 Jingbaji Road, Shizhong District, Jinan 250000, Shandong Province, China. 18364155005@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
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/
World J Gastrointest Oncol. Aug 15, 2025; 17(8): 107412 Published online Aug 15, 2025. doi: 10.4251/wjgo.v17.i8.107412
Role of circulating tumor DNA methylation in gastric cancer initiation and progression: A comprehensive review
Hai-Yu Huang, Jiang Lan, Wei Zhuang
Hai-Yu Huang, Department of Hematology and Oncology, Fengdu General Hospital, Chongqing 408200, China
Jiang Lan, Department of General Surgery, The Affiliated Dazu's Hospital of Chongqing Medical University, Chongqing 402360, China
Wei Zhuang, Department of Intensive Care Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250000, Shandong Province, China
Co-corresponding authors: Jiang Lan and Wei Zhuang.
Author contributions: Huang HY contributed to the conceptualization, data curation, and drafting of the manuscript; Lan J was responsible for the methodology design, literature review, and revision of the manuscript; Zhuang W supervised the study, provided critical revisions to the manuscript, and managed the project; Lan J and Zhuang W contributed equally to this work as co-corresponding authors; all the authors have read and approved the final manuscript.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest related to this manuscript.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wei Zhuang, MD, Department of Intensive Care Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No. 1 Jingbaji Road, Shizhong District, Jinan 250000, Shandong Province, China. 18364155005@163.com
Received: March 26, 2025 Revised: May 5, 2025 Accepted: June 19, 2025 Published online: August 15, 2025 Processing time: 141 Days and 15 Hours
Abstract
Circulating tumor DNA (ctDNA) is the free DNA released by tumor or circulating tumor cells, which is associated with many tumor characteristics and can be used as a biomarker for early screening, monitoring, prognosis, and prediction of therapeutic response in patients with cancer. The field of gastric cancer is very attractive because there are no high-quality screening, monitoring, or prediction methods. Gastric cancer is characterized by great tumor heterogeneity, great differences in genetic and epigenetic characteristics among different subgroups of gastric cancer, and high sensitivity and specificity of methylated ctDNA, which is conducive to the identification of tumor genotypes and the formulation of accurate diagnostic and treatment strategies. In addition, many studies have confirmed that methylated DNA has unique advantages in predicting treatment response, adjuvant therapy, and drug resistance and can be used to increase the efficacy of chemotherapy regimens, improve the chemotherapy response of patients in the future, and even treat multidrug resistance. However, methylated ctDNA also faces many problems, such as low sensitivity and specificity in a single target, limited association between some gastric cancer subtypes and ctDNA, risk of off-target effects, and lack of large-sample and high-quality clinical research evidence. This review mainly summarizes the current research on the DNA methylation of circulating gastric cancer tumors and links these findings with the early screening of gastric cancer, recurrence monitoring, and potential treatment opportunities. With the advancement of technology and the deepening of cross-research between doctors and professionals, ctDNA detection will reveal more disease information and become an important basis for the field of gastric cancer and precision medicine treatment.
Core Tip: Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker for early cancer detection and monitoring. Aberrant DNA methylation is one of the earliest and most frequent epigenetic alterations in gastric cancer. This review summarizes recent advances in understanding the role of ctDNA methylation in gastric cancer initiation and progression, and its potential clinical applications. We highlight the advantages of ctDNA methylation analysis in disease diagnosis, prognosis prediction, and therapeutic monitoring. A better understanding of ctDNA methylation dynamics may provide new insights into personalized medicine and improve outcomes in patients with gastric cancer.
