Systematic Reviews
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Jul 27, 2025; 17(7): 107110
Published online Jul 27, 2025. doi: 10.4240/wjgs.v17.i7.107110
Multi-omics perspectives for gastrointestinal malignancy: A systematic review
Thai-Hau Koo, Yi-Lin Lee, Xue-Bin Leong, Firdaus Hayati, Mohd Hazeman Zakaria, Andee Dzulkarnaen Zakaria
Thai-Hau Koo, Department of Internal Medicine, University Sains Malaysia Specialist Hospital, Kubang Kerian 16150, Kelantan, Malaysia
Yi-Lin Lee, Xue-Bin Leong, School of Medical Sciences, University Sains Malaysia, Health Campus, Kubang Kerian 16150, Kelantan, Malaysia
Firdaus Hayati, Department of Surgery, Faculty of Medicine and Health Sciences, University Malaysia Sabah, Kota Kinabalu 88400, Sabah, Malaysia
Mohd Hazeman Zakaria, Department of Radiology, Faculty of Medicine and Health Science, University Putra Malaysia, Serdang 43400, Selangor, Malaysia
Andee Dzulkarnaen Zakaria, Department of Surgery, School of Medical Sciences, University Sains Malaysia, Kota Bharu 16150, Kelantan, Malaysia
Co-first authors: Thai-Hau Koo and Yi-Lin Lee.
Author contributions: Koo TH and Lee YL made equal contributions as co-first authors. Koo TH, Hayati F, and Zakaria AD designed the overall concept and outline of the manuscript; Lee YL, Leong XB, and Zakaria MH contributed to the discussion and design of the manuscript; Koo TH, Lee YL, Leong XB, Zakaria MH, and Zakaria AD contributed to the writing and editing the manuscript, illustrations, and review of literature; and all authors have read and approved the final manuscript.
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.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Andee Dzulkarnaen Zakaria, MD, Professor, Department of Surgery, School of Medical Sciences, University Sains Malaysia, Jalan Raja Perempuan Zainab 2, Kubang Kerian, Kota Bharu 16150, Kelantan, Malaysia. andee@usm.my
Received: March 17, 2025
Revised: April 24, 2025
Accepted: May 28, 2025
Published online: July 27, 2025
Processing time: 130 Days and 7.9 Hours
Abstract
BACKGROUND

Gastrointestinal (GI) malignancies, including gastric and colorectal cancers, remain one of the primary contributors to cancer-related illness and death globally. Despite the availability of conventional diagnostic tools, early detection and personalized treatment remain significant clinical challenges. Integrated multi-omics methods encompassing genomic, transcriptomic, proteomic, metabolomic, and microbiome profiles have emerged as powerful tools for advancing precision oncology, improving diagnostic accuracy, and informing therapeutic strategies.

AIM

To investigate the application of multi-omics approaches in the early detection, risk stratification, treatment optimization, and biomarker discovery of GI malignancies.

METHODS

The systematic review process was conducted in accordance with the PRISMA 2020 guidelines. Five databases, PubMed, ScienceDirect, Scopus, ProQuest, and Web of Science, were searched for studies published in English from 2015 onwards. Eligible studies involved human subjects and focused on multi-omics integration in GI cancers, including biomarker identification, tumor microenvironment analysis, tumor heterogeneity, organoid modeling, and artificial intelligence (AI)-driven analytics. Data extraction included study characteristics, omics modalities, clinical applications, and evaluation of study quality conducted with the Cochrane risk of bias 2.0 instrument.

RESULTS

A total of 17196 initially identified articles, 20 met the inclusion criteria. The findings highlight the superiority of multi-omics platforms over traditional biomarkers (e.g., carcinoembryonic antigen and carbohydrate antigen 19-9 in detecting early stage GI cancers. Key applications include the identification of circulating tumor DNA, extracellular vesicles, lipidomic and proteomic signatures, and the adoption of AI algorithms to enhance diagnostic precision. Multi-omics analysis has also revealed the mechanisms of immune modulation, tumor microenvironment regulation, metastatic behavior, and drug resistance. Organoid models and microbiota profiling have contributed to personalized therapeutic strategies and immunotherapy optimization.

CONCLUSION

Multi-omics approaches offer significant advancements in the early diagnosis, prognostic evaluation, and personalized treatment of GI malignancies. Their integration with AI analytics, organoid biobanking, and microbiota modulation provides a pathway for precision oncology research.

Keywords: Proteomic; Multi-omics; Gastrointestinal malignancy; Precision oncology; Biomarker discovery; Therapeutic resistance

Core Tip: Gastrointestinal malignancies present substantial diagnostic and therapeutic challenges due to their molecular complexity. This systematic review highlights how comprehensive omics strategies incorporating genomic, transcriptomic, proteomic, and metabolomic data and epigenomics, integrated with machine learning and artificial intelligence, can revolutionize precision oncology. These strategies enable early detection through biomarkers like circulating tumor DNA and extracellular vesicles, enhance risk stratification, and uncover mechanisms of drug resistance and tumor heterogeneity, paving the way for individualized gastrointestinal cancer therapies.