{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T19:21:32Z","timestamp":1789413692304,"version":"build-2803163510"},"reference-count":184,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Colorectal cancer (CRC) is a biologically heterogeneous disease in which single-omics analyses incompletely capture the cross-layer mechanisms underlying tumor progression, immune evasion, and therapeutic resistance. This review critically examines how the integration of genomics, transcriptomics, proteomics, metabolomics, and microbiome profiling is redefining CRC biology and precision oncology. Landmark integrative efforts, including TCGA analyses of 276 colorectal cancer samples, CPTAC proteogenomic profiling of 95 tumors, and recent whole-genome sequencing studies of 2023 CRC cases, have refined molecular subtyping, expanded the driver landscape, and revealed clinically relevant discordance between mRNA abundance and protein activity. Integrative studies further show that oncogenic signaling may be driven by post-transcriptional and post-translational regulation, while spatially resolved profiling and microbiome\u2013metabolite analyses are uncovering previously obscured tumor\u2013microenvironment interactions. We also discuss how artificial intelligence-based approaches, including factor analysis, deep learning, graph-based models, and explainable AI, are improving subtype classification, biomarker discovery, and treatment-response prediction, with particular relevance to microsatellite instability-high and early-onset CRC. Finally, we critically evaluate the principal barriers to clinical translation, including batch effects, cross-platform variability, limited external validation, regulatory constraints, and cost, and outline priorities for building reproducible, clinically deployable multi-omics pipelines for CRC management.<\/jats:p>","DOI":"10.3390\/cancers18101504","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T14:05:46Z","timestamp":1778162746000},"page":"1504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Multi Omics Integration in Colorectal Cancer: From Molecular Insights to Precision Oncology"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4280-0084","authenticated-orcid":false,"given":"Zuoliang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery, Affiliated Hospital of North Sichuan Medical College, Maoyuan South Road, Shunqing District, Nanchong 637000, China"},{"name":"School of Graduate Studies, Post Graduate Centre, Management and Science University, Seksyen 13, Shah Alam 40100, Selangor, Malaysia"},{"name":"Institute of Hepatobiliary Pancreatic Intestinal Diseases, North Sichuan Medical College, Maoyuan South Road, Shunqing District, Nanchong 637000, China"},{"name":"National Clinical Key Specialty (General Surgery), Sub-Center of National Clinical Research Center for Digestive Diseases, Sichuan Clinical Research Center for Digestive Diseases, Nanchong 637000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2709-6754","authenticated-orcid":false,"given":"Mia Yang","family":"Ang","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Allied Health Science, Faculty of Health and Life Sciences, Management and Science University (MSU), University Drive, Off Persiaran Olahraga, Section 13, Shah Alam 40100, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9793-5616","authenticated-orcid":false,"given":"Chin Siang","family":"Kue","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Allied Health Science, Faculty of Health and Life Sciences, Management and Science University (MSU), University Drive, Off Persiaran Olahraga, Section 13, Shah Alam 40100, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: Globocan Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. 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