Publication Name	World Journal of Gastroenterology
Manuscript ID	115301
Country	China

Category	Medicine, Research & Experimental
Manuscript Type	Basic Study
Article Title	ICAM2 loss drives 5-fluorouracil resistance via TGF-β/Smad/SP1/PTN-dependent apoptosis evasion and macrophage remodeling in gastric cancer
Manuscript Source	Unsolicited Manuscript
All Author List	Xiao-Cheng Tang, Zi-Jian Chen, Chun-Yu Chen, Jun Qiu, Jin-Tuan Huang, Rong-Chang Tan, Wei-Yao Li, Hao Chen and Zu-Li Yang
Funding Agency and Grant Number	Funding Agency Grant Number National Natural Science Foundation of China 81802322 National Natural Science Foundation of China 81902949 Natural Science Foundation of Guangdong Province 2020A1515011362 Natural Science Foundation of Guangdong Province 2022A1515010262 Science and Technology Program of Guangdong Province 2022A0505030004
Corresponding Author	Zu-Li Yang, Additional Professor, Chief Physician, Department of General Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, People's Republic of China. yangzuli@mail.sysu.edu.cn., Guangzhou 510655, Guangdong Province, China. yangzuli@mail.sysu.edu.cn
Key Words	Biomarker; Chemoresistance; Apoptosis; Intercellular adhesion molecule 2; Tumor microenvironment
Core Tip	Intercellular adhesion molecule 2 (ICAM2) is both a predictive biomarker and a mechanistic mediator of chemoresistance in advanced gastric cancer. Low serum and tissue ICAM2 identify neoadjuvant nonresponders and predict shorter survival. Functionally, ICAM2 loss increases 5-fluorouracil (5-FU) resistance by impairing caspase-dependent apoptosis and remodeling an immunosuppressive, M2-biased macrophage milieu. Mechanistically, ICAM2 loss activates TGF-β/Smad signaling, which upregulates the transcription factor SP1; SP1 then directly pleiotrophin (PTN). Targeting TGF-β suppresses PTN and restores 5-FU sensitivity in preclinical models, positioning the ICAM2/TGF-β/Smad/SP1/PTN axis as a clinically actionable pathway.
Citation	Tang XC, Chen ZJ, Chen CY, Qiu J, Huang JT, Tan RC, Li WY, Chen H, Yang ZL. ICAM2 loss drives 5-fluorouracil resistance via TGF-β/Smad/SP1/PTN-dependent apoptosis evasion and macrophage remodeling in gastric cancer. World J Gastroenterol 2025; In press

Received	2025-10-16 15:47
Peer-Review Started	2025-10-16 15:47
First Decision by Editorial Office Director	2025-10-31 09:18
Return for Revision	2025-10-31 09:18
Revised	2025-11-13 13:00
Publication Fee Transferred	2025-11-19 04:07
Second Decision by Editor	2025-12-08 02:34
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2025-12-08 06:27
Articles in Press	2025-12-08 06:27
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1007-9327 (print) and 2219-2840 (online)
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