Publication Name	World Journal of Gastroenterology
Manuscript ID	108990
Country	China

Category	Pathology
Manuscript Type	Basic Study
Article Title	Clinicopathological significance of histological diversity in gastric adenocarcinoma with primitive enterocyte phenotype: A methylation-driven aggressive entity
Manuscript Source	Unsolicited Manuscript
All Author List	Hou-Qiang Li, Lan-Qing Zheng, Wen-Tao Huang, Xun-Bin Yu, Xia Zhang, Lan Lin, Shan-Shan Lv, Xi-Yao Yan and Xiao-Yan Chen
Funding Agency and Grant Number	Funding Agency Grant Number Startup Fund for Scientific Research, Fujian Medical University, No. 2020QH1168 Fujian Provincial Science and Technology Innovation Joint Funds No. 2024Y9023 Fujian Provincial Natural Science Foundation of China No. 2024J011644
Corresponding Author	Hou-Qiang Li, Researcher, Department of Pathology, Fuzhou University Affiliated Provincial Hospital, No. 134 East Street, Fuzhou 350001, Fujian Province, China. docli254@163.com
Key Words	Gastric cancer; Gastric adenocarcinoma with enteroblastic differentiation; Hepatoid adenocarcinoma; Alpha-fetoprotein; Bioinformatics; Methylation
Core Tip	Gastric adenocarcinoma with primitive enterocyte phenotype (GAPEP) exhibits aggressive behavior and diverse morphologies, including tubular-papillary and solid types, which necessitate integrated histopathological, immunohistochemical, and molecular experiments for accurate identification. This study highlighted GAPEP’s methylation-driven pathogenesis, with methylation dysregulation (e.g., DNMT3A/B/L, TET1/3 and EZH2 upregulation). Gastric adenocarcinoma with enteroblastic differentiation and hepatoid adenocarcinoma shared similar clinicopathological and genetic features, suggesting a common origin. Targeting methylation pathways (e.g., DNMT inhibitors) offers potential therapeutic avenues for this lethal cancer, emphasizing the critical role of epigenetic mechanisms in the pathogenesis of GAPEP.
Citation	Li HQ, Zheng LQ, Huang WT, Yu XB, Zhang X, Lin L, Lv SS, Yan XY, Chen XY. Clinicopathological significance of histological diversity in gastric adenocarcinoma with primitive enterocyte phenotype: A methylation-driven aggressive entity. World J Gastroenterol 2025; In press

Received	2025-04-28 08:16
Peer-Review Started	2025-04-28 08:17
To Make the First Decision
Return for Revision	2025-05-14 03:43
Revised	2025-05-22 13:06
Second Decision	2025-06-23 02:41
Accepted by Journal Editor-in-Chief
Accepted by Executive Editor-in-Chief	2025-06-23 05:15
Articles in Press	2025-06-23 05:15
Publication Fee Transferred	2025-05-29 00:15
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1007-9327 (print) and 2219-2840 (online)
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: http://creativecommons.org/Licenses/by-nc/4.0/
Copyright	© The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Permissions	For details, please visit: http://www.wjgnet.com/bpg/gerinfo/207
Publisher	Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Website	http://www.wjgnet.com