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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Gastrointest Oncol. Dec 15, 2026; 18(12): 126494
Published online Dec 15, 2026. doi: 10.4251/wjgo.126494
cfDNA methylation highlights neuro-immune crosstalk as a key correlate of pathological response to neoadjuvant immunotherapy in gastric cancer
Chen-Bin Lv, Lin-Yan Tong, Yi-Chen Cai, Wei-Ping Lin, Yu-Qin Sun, Yong-Bin Zhang, Wei-Ming Zeng, Li-Sheng Cai, Qiu-Xian Chen
Chen-Bin Lv, Lin-Yan Tong, Yu-Qin Sun, Yong-Bin Zhang, Wei-Ming Zeng, Li-Sheng Cai, Qiu-Xian Chen, Department of Gastric Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, Fujian Province, China
Yi-Chen Cai, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, School of Life Sciences, Xiamen University, Xiamen 361000, Fujian Province, China
Wei-Ping Lin, Fujian Medical University Union Hospital, Fuzhou 350000, Fujian Province, China
Co-first authors: Chen-Bin Lv, Lin-Yan Tong.
Co-corresponding authors: Li-Sheng Cai and Qiu-Xian Chen.
Author contributions: Lv CB and Tong LY contributed equally to this article, they are the co-first authors of this manuscript; Lv CB and Chen QX designed the study and acquired funding; Lv CB, Tong LY, Cai YC, and Lin WP were responsible for developing the methodology; Sun YQ, Zhang YB, and Zeng WM participated in the formal analysis and investigation; Lv CB, Tong LY, Cai YC, and Lin WP wrote the original draft; Lv CB, Tong LY, Cai LS, and Chen QX participated in the review and editing; Cai LS and Chen QX contributed equally to this article, they are the co-corresponding authors of this manuscript; and all authors have read and approved the final version of the manuscript.
AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.
Supported by the Natural Science Foundation of Fujian Province, No. 2024J011567; and Climbing Project of Doctors’ Studio of Zhangzhou Hospital Affiliated to Fujian Medical University, No. PDA202204.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Zhangzhou Hospital Affiliated to Fujian Medical University, approval No. 2024KYB068.
Informed consent statement: Informed consent was obtained from all subjects and/or their legal guardians. All procedures were conducted in accordance with the Declaration of Helsinki and relevant guidelines and regulations.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The dataset analyzed for this study is available from the corresponding author on reasonable request.
Corresponding author: Li-Sheng Cai, Chief Physician, Associate Professor, Department of Gastric Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, No. 59 Sheng-li Road, Zhangzhou 363000, Fujian Province, China. wxccls2024@163.com
Received: August 6, 2026
Revised: September 8, 2026
Accepted: October 29, 2026
Published online: December 15, 2026
Processing time: 96 Days and 9 Hours
Core Tip

Core Tip: This proof-of-concept study explored cell-free DNA methylation profiles associated with major pathological response to neoadjuvant immunotherapy in gastric cancer. CpG-island-enriched profiling identified 37185 nominally significant differentially methylated sites, of which 8904 remained significant after false discovery rate correction; functional enrichment of these false discovery rate-confirmed differentially methylated sites implicated neuroactive ligand-receptor interaction and G protein-coupled receptor signaling rather than conventional T-cell pathways. Three CpG sites were prioritized as exploratory candidates. These findings generate a testable hypothesis that baseline neuro-immune signaling may be associated with immunotherapy response through epigenetic mechanisms, offering a new biological perspective and candidate markers for future validation.

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