Deciphering the Role of DNA Methylation-Driven Genes in Rectal Cancer: Insights into Prognostic Modeling and Mechanistic Pathways

Deciphering the Role of DNA Methylation-Driven Genes in Rectal Cancer: Insights into Prognostic Modeling and Mechanistic Pathways | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Deciphering the Role of DNA Methylation-Driven Genes in Rectal Cancer: Insights into Prognostic Modeling and Mechanistic Pathways Weipeng Liu, Lugao Tian, Yongbin Zheng This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5406298/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background DNA methylation alterations play a crucial role in rectal cancer development. This study identifies and characterizes DNA methylation-driven genes in the TCGA-READ cohort, exploring their association with rectal cancer development and the underlying mechanism. Methods DNA methylation-driven genes were identified using MethylMix package and subjected to gene ontology (GO) enrichment analysis via cluster profiler package. Prognostic model development involved Lasso regression and ten-fold cross-validation, followed by performance evaluation using Kaplan-Meier survival curves, time-dependent ROC curves, calibration curves, and decision curve analysis. Cancer-promoting mechanism underlying high risk score group was clarified through gene set enrichment analysis (GSEA) and multi-algorithm-based immune infiltration analyses. Results GO enrichment analysis highlighted significant functional terms based on 490 DNA methylation-driven genes, implicating Wnt signaling and cell fate commitment in rectal cancer development. The developed prognostic model, consisting of CCNI2, LINC00899, and ST6GALNAC1, exhibited high predictive accuracy. Differential gene expression analysis identified 89 underexpressed genes in the high-risk score group, with SULF1 identified as a hub gene. The negative regulation process of malignant tumor-associated pathways is suppressed, and the decreased infiltration abundance of cytotoxic cells, such as NK cells, may represent a potential mechanism for the poor prognosis observed in the high-risk score group. Conclusions Our findings elucidate the landscape of DNA methylation-driven genes in rectal cancer. These insights contribute to a deeper understanding of rectal cancer progression and provide potential targets for therapeutic intervention. DNA Methylation Rectal Cancer Prognostic Model Enrichment Analysis Immune Infiltration Full Text Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5406298","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":414612605,"identity":"f694ba30-8c6e-494d-b9a6-5f38d3b8568e","order_by":0,"name":"Weipeng Liu","email":"","orcid":"","institution":"Renmin Hospital of Wuhan University: Wuhan University Renmin Hospital","correspondingAuthor":false,"prefix":"","firstName":"Weipeng","middleName":"","lastName":"Liu","suffix":""},{"id":414612606,"identity":"580b1361-3658-48bc-ab2c-8babd9a7863b","order_by":1,"name":"Lugao Tian","email":"","orcid":"","institution":"China Three Gorges University","correspondingAuthor":false,"prefix":"","firstName":"Lugao","middleName":"","lastName":"Tian","suffix":""},{"id":414612607,"identity":"00da73e1-d1fb-41c4-8ed7-251dd753a707","order_by":2,"name":"Yongbin Zheng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9ElEQVRIiWNgGAWjYJACZgYDBhBiYPjAcABEGRCvhXEG8Vqgyph5iNFicLz38OuCgjv25uxAhm3bncQG9uZtEgw1d3BrOXMuzXqGwTNmyx4gI7ftWWIDz7EyCYZjz3BruZFjZsxjcJgNzMjddjixQSLHTIKx4TBBLTwG99+YGVuCtMi/IajF+DFQi4TBDR7jx4xgW3jwa5E8c8aMeYbBYQODMzlmjL3/Dhu38aQVWyQcw62F73iP8eeCP4ftDY6fMf7w48xh2X72wxtvfKjBrUXhAAObBJQNYbCBiAScGhgY5BsYmD9A2XDGKBgFo2AUjAIUAAB88FsqcHHzJwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0009-0000-2739-7237","institution":"Wuhan University Renmin Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yongbin","middleName":"","lastName":"Zheng","suffix":""}],"badges":[],"createdAt":"2024-11-07 03:12:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5406298/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5406298/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":78476103,"identity":"3deb2cbe-c9de-40e0-91d7-098d4a302179","added_by":"auto","created_at":"2025-03-13 17:02:43","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2167291,"visible":true,"origin":"","legend":"","description":"","filename":"DecipheringtheRoleofDNAMethylationDriven.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5406298/v1_covered_48246e95-575e-4025-8ccc-dfc19da49244.pdf"}],"financialInterests":"","formattedTitle":"Deciphering the Role of DNA Methylation-Driven Genes in Rectal Cancer: Insights into Prognostic Modeling and Mechanistic Pathways","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"DNA Methylation, Rectal Cancer, Prognostic Model, Enrichment Analysis, Immune Infiltration","lastPublishedDoi":"10.21203/rs.3.rs-5406298/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5406298/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eDNA methylation alterations play a crucial role in rectal cancer development. This study identifies and characterizes DNA methylation-driven genes in the TCGA-READ cohort, exploring their association with rectal cancer development and the underlying mechanism.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eDNA methylation-driven genes were identified using MethylMix package and subjected to gene ontology (GO) enrichment analysis via cluster profiler package. Prognostic model development involved Lasso regression and ten-fold cross-validation, followed by performance evaluation using Kaplan-Meier survival curves, time-dependent ROC curves, calibration curves, and decision curve analysis. Cancer-promoting mechanism underlying high risk score group was clarified through gene set enrichment analysis (GSEA) and multi-algorithm-based immune infiltration analyses.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eGO enrichment analysis highlighted significant functional terms based on 490 DNA methylation-driven genes, implicating Wnt signaling and cell fate commitment in rectal cancer development. The developed prognostic model, consisting of CCNI2, LINC00899, and ST6GALNAC1, exhibited high predictive accuracy. Differential gene expression analysis identified 89 underexpressed genes in the high-risk score group, with SULF1 identified as a hub gene. The negative regulation process of malignant tumor-associated pathways is suppressed, and the decreased infiltration abundance of cytotoxic cells, such as NK cells, may represent a potential mechanism for the poor prognosis observed in the high-risk score group.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOur findings elucidate the landscape of DNA methylation-driven genes in rectal cancer. These insights contribute to a deeper understanding of rectal cancer progression and provide potential targets for therapeutic intervention.\u003c/p\u003e","manuscriptTitle":"Deciphering the Role of DNA Methylation-Driven Genes in Rectal Cancer: Insights into Prognostic Modeling and Mechanistic Pathways","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-14 12:00:20","doi":"10.21203/rs.3.rs-5406298/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fd45ff89-3c23-490f-8a9a-dbb78b266e91","owner":[],"postedDate":"February 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-13T16:54:36+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-14 12:00:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5406298","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5406298","identity":"rs-5406298","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}