Publication Name	World Journal of Gastroenterology
Manuscript ID	124207
Country	China

Category	Gastroenterology & Hepatology
Manuscript Type	Prospective Study
Article Title	Integrating metabolomics, clinical factors, and genetic risk for colorectal cancer risk prediction: Model development and internal-external cross-validation
Manuscript Source	Unsolicited Manuscript
All Author List	Liang-Tang Zeng, Jun-Nan Hu, Ming-Hui Pang, Qin-Xing Cao, Neng-Yi Hou and Feng Liu
Funding Agency and Grant Number	Funding Agency Grant Number Special Project for Clinical Research in Health Industry of Shanghai Municipal Health Commission No. 202540026 Cultivation Grant for Clinical and Basic Integration Research of Shanghai Tenth People’s Hospital No. SYYYRH2025006
Corresponding Author	Feng Liu, Chief Physician, Full Professor, Digestive Endoscopy Center, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, No. 301 Yanchang Road, Shanghai 200072, China. 1905041@tongji.edu.cn
Key Words	Plasma metabolomics; Colorectal cancer; Risk prediction; Risk stratification; Polygenic risk score
Core Tip	Using data from 468095 UK Biobank participants, we evaluated 325 nuclear magnetic resonance-based plasma metabolic markers and developed a seven-feature metabolomic risk score for incident colorectal cancer. The score stratified long-term risk and modestly improved prediction when added to an adapted QCancer clinical model and a polygenic risk score. Internal-external cross-validation across 10 geographical clusters supported consistency and geographical transportability within the UK Biobank. These findings suggest that metabolomics may complement, rather than replace, established clinical and genetic risk assessment. Independent external validation and cost-effectiveness evaluation are required before clinical implementation.
Citation	Zeng LT, Hu JN, Pang MH, Cao QX, Hou NY, Liu F. Integrating metabolomics, clinical factors, and genetic risk for colorectal cancer risk prediction: Model development and internal-external cross-validation. World J Gastroenterol 2026; In press

Received	2026-06-09 05:50
Peer-Review Started	2026-06-09 05:50
First Decision by Editorial Office Director
Return for Revision	2026-07-01 01:12
Revised	2026-07-14 04:33
Publication Fee Transferred	2026-07-21 15:19
Second Decision by Editor	2026-07-27 02:43
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-07-27 09:51
Articles in Press	2026-07-27 09:51
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 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.
Copyright	©Author(s) (or their employer(s)) 2026. No commercial re-use. See Permissions. Published by Baishideng Publishing Group Inc.
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