Zhou LJ, Hao XY, Wang C, Ren NN, Wang YG. Comprehensive modeling of the Correa cascade in precancerous lesions of gastric cancer: Leveraging animal, cellular, and organoid systems for translational insights. World J Gastrointest Oncol 2026; 18(3): 113757 [DOI: 10.4251/wjgo.v18.i3.113757]
Corresponding Author of This Article
Ning-Ning Ren, PhD, Department of Spleen and Stomach, Beijing University of Chinese Medicine Third Affiliated Hospital, No. 11 North Third Ring East Road, Chaoyang District, Beijing 100029, China. renning2024@163.com
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Gastroenterology & Hepatology
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Systematic Reviews
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Mar 15, 2026 (publication date) through Mar 12, 2026
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World Journal of Gastrointestinal Oncology
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Zhou LJ, Hao XY, Wang C, Ren NN, Wang YG. Comprehensive modeling of the Correa cascade in precancerous lesions of gastric cancer: Leveraging animal, cellular, and organoid systems for translational insights. World J Gastrointest Oncol 2026; 18(3): 113757 [DOI: 10.4251/wjgo.v18.i3.113757]
World J Gastrointest Oncol. Mar 15, 2026; 18(3): 113757 Published online Mar 15, 2026. doi: 10.4251/wjgo.v18.i3.113757
Comprehensive modeling of the Correa cascade in precancerous lesions of gastric cancer: Leveraging animal, cellular, and organoid systems for translational insights
Li-Jie Zhou, Xin-Yu Hao, Chen Wang, Ning-Ning Ren, Yan-Gang Wang
Li-Jie Zhou, Chen Wang, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing 100029, China
Xin-Yu Hao, Department of Traditional Chinese Medicine, Peking University Third Hospital, Beijing 100191, China
Ning-Ning Ren, Yan-Gang Wang, Department of Spleen and Stomach, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing 100029, China
Yan-Gang Wang, Department of Spleen and Stomach, Hebei Province Hospital of Traditional Chinese Medicine, Shijiazhuang 050011, Hebei Province, China
Co-first authors: Li-Jie Zhou and Xin-Yu Hao.
Co-corresponding authors: Ning-Ning Ren and Yan-Gang Wang.
Author contributions: Zhou LJ and Hao XY designed the research study and analyzed the data, and contributed equally as co-first authors; Zhou LJ drafted the manuscript; Wang C revised the manuscript; Ren NN and Wang YG provided critical review and editing, and contributed equally as co-corresponding authors. All authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 82575015; Beijing Natural Science Foundation, No. 7232281; and Fundamental Research Funds for the Central Universities, No. 2025-JYB-JBGS-001.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Ning-Ning Ren, PhD, Department of Spleen and Stomach, Beijing University of Chinese Medicine Third Affiliated Hospital, No. 11 North Third Ring East Road, Chaoyang District, Beijing 100029, China. renning2024@163.com
Received: September 3, 2025 Revised: November 28, 2025 Accepted: January 4, 2026 Published online: March 15, 2026 Processing time: 190 Days and 23.2 Hours
Abstract
BACKGROUND
Precancerous lesions of gastric cancer (PLGC), including chronic atrophic gastritis, intestinal metaplasia, and dysplasia, constitute key transitional stages in the Correa cascade toward gastric cancer. Understanding these stages is essential for early detection, prevention, and therapeutic intervention.
AIM
To provide a comprehensive and critical overview of current animal, cellular, and organoid models used in PLGC research, emphasizing their applications, translational relevance, and emerging technologies.
METHODS
A scoping systematic review was performed according to the PRISMA-ScR framework. Literature was identified from PubMed and Web of Science up to June 2025 using predefined keywords and Boolean operators. Eligible studies included experimental reports describing animal, cellular, or organoid models of PLGC. Two authors independently screened titles, abstracts, and full texts, and relevant data were charted and synthesized narratively.
RESULTS
This study delineates the modeling strategies for PLGC across various platforms. Animal models, including chemical induction with N-methyl-N’-nitro-N-nitrosoguanidine, N-nitroso-N-methylurea, Helicobacter pylori infection, transgenic approaches, and composite modeling, recapitulate the histopathological spectrum of PLGC and facilitate mechanistic discovery. Cellular models simulate chronic inflammation and carcinogen exposure, enabling high-throughput mechanistic screening. Gastric organoids derived from patients or animals offer a physiologically relevant three-dimensional culture system, reproducing epithelial transformation and Helicobacter pylori-induced pathology, with recent advances in co-culture systems and immune-organoid interactions. Integration of gene editing, single-cell transcriptomics, and organoid-on-chip platforms is expected to further refine PLGC modeling and accelerate clinical translation.
CONCLUSION
Integrated PLGC models provide a robust framework for elucidating the cellular and molecular basis of early gastric tumorigenesis. Their continued evolution will enhance biomarker discovery, immunologic investigation, and therapeutic development.
Core Tip: Precancerous lesions of gastric cancer (GC), including atrophic gastritis, intestinal metaplasia, and dysplasia, represent the pivotal transition in the Correa cascade. Accurate modeling of these lesions is crucial for dissecting early gastric tumorigenesis and identifying chemopreventive strategies. This scoping study systematically summarizes current precancerous lesions of GC models, including chemical- and infection-induced animal systems, transformed gastric epithelial cell lines, and organoid platforms derived from stem cells. We highlight their advantages, limitations, and recent advances such as genome editing, single-cell technologies, and immune co-culture. These insights provide a roadmap for selecting appropriate experimental systems and accelerating translational research in early GC prevention and therapy.
