{"paper_id":"44bf7a01-7283-4f7d-b4f3-6d06e080b597","body_text":"Identification and Validation of RNA Modification-Related Biomarkers in Dilated cardiomyopathy | 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 Article Identification and Validation of RNA Modification-Related Biomarkers in Dilated cardiomyopathy zhe wang, xuanzheng fang, xin Wang, longmei Liu, Lei Yao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8221884/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 The role of RNA modification-related genes (RMRGs) in Dilated cardiomyopathy (DCM) remains unclea. This study aimed to explore their contributions to HF pathogenesis. Methods Transcriptomic (GSE57338 and GSE42955) and single-cell RNA sequencing data (scRNA-seq) (GSE183852) were analyzed to identify RMRG-based biomarkers. Through integrating differential expression profiling, weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) networks, and machine learning algorithms, potential biomarkers were systematically identified. Predictive nomogram models targeting HF were established, complemented by subsequent functional enrichment studies, immune cell infiltration characterization, and therapeutic compound screening. Key cellular populations were determined through scRNA-seq technology, while reverse transcription quantitative PCR (RT-qPCR) served to clinically verify the expression patterns of candidate biomarkers. Results FURIN, STAT3, and BCL6 were identified as biomarkers. Enrichment analysis linked these biomarkers to pathways related to energy metabolism and immune regulation. Immune cell infiltration, specifically activated dendritic cells (aDCs), showed significant differences between HF and control groups ( p < 0.05). Vincristine sulfate and ciglitazone were suggested as potential therapeutic agents for DCM. scRNA-seq identified endothelial cells and fibroblasts as key cells, with biomarkers showing distinct dynamic expression during their differentiation. RT-qPCR validation demonstrated markedly reduced expression of FURIN, STAT3, and BCL6 in HF patients relative to controls, aligning with computational predictions. Conclusions These three genes—FURIN, STAT3, and BCL6—emerged as RM-associated molecular signatures in HF pathophysiology, potentially informing novel therapeutic and preventive approaches. Health sciences/Biomarkers Health sciences/Cardiology Biological sciences/Computational biology and bioinformatics Health sciences/Diseases Heart failure RNA modification Nomogram Endothelial cells Fibroblasts Full Text Additional Declarations No competing interests reported. Supplementary Files SUPPLE1.zip 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-8221884\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Article\",\"associatedPublications\":[],\"authors\":[{\"id\":561276590,\"identity\":\"e51ba7fa-ce08-4cab-a31a-ce4746be7cef\",\"order_by\":0,\"name\":\"zhe wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Shanxi Cardiovascular Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"zhe\",\"middleName\":\"\",\"lastName\":\"wang\",\"suffix\":\"\"},{\"id\":561276595,\"identity\":\"5f22a34f-3d87-447c-b1c9-1cc30d6c5ddc\",\"order_by\":1,\"name\":\"xuanzheng 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cardiomyopathy\",\"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\":\"info@researchsquare.com\",\"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\":\"Heart failure, RNA modification, Nomogram, Endothelial cells, Fibroblasts\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-8221884/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-8221884/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eBackground\\u003c/h2\\u003e \\u003cp\\u003eThe role of RNA modification-related genes (RMRGs) in Dilated cardiomyopathy (DCM) remains unclea. This study aimed to explore their contributions to HF pathogenesis.\\u003c/p\\u003e\\u003ch2\\u003eMethods\\u003c/h2\\u003e \\u003cp\\u003eTranscriptomic (GSE57338 and GSE42955) and single-cell RNA sequencing data (scRNA-seq) (GSE183852) were analyzed to identify RMRG-based biomarkers. Through integrating differential expression profiling, weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) networks, and machine learning algorithms, potential biomarkers were systematically identified. Predictive nomogram models targeting HF were established, complemented by subsequent functional enrichment studies, immune cell infiltration characterization, and therapeutic compound screening. Key cellular populations were determined through scRNA-seq technology, while reverse transcription quantitative PCR (RT-qPCR) served to clinically verify the expression patterns of candidate biomarkers.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e \\u003cp\\u003eFURIN, STAT3, and BCL6 were identified as biomarkers. Enrichment analysis linked these biomarkers to pathways related to energy metabolism and immune regulation. Immune cell infiltration, specifically activated dendritic cells (aDCs), showed significant differences between HF and control groups (\\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05). Vincristine sulfate and ciglitazone were suggested as potential therapeutic agents for DCM. scRNA-seq identified endothelial cells and fibroblasts as key cells, with biomarkers showing distinct dynamic expression during their differentiation. RT-qPCR validation demonstrated markedly reduced expression of FURIN, STAT3, and BCL6 in HF patients relative to controls, aligning with computational predictions.\\u003c/p\\u003e\\u003ch2\\u003eConclusions\\u003c/h2\\u003e \\u003cp\\u003eThese three genes\\u0026mdash;FURIN, STAT3, and BCL6\\u0026mdash;emerged as RM-associated molecular signatures in HF pathophysiology, potentially informing novel therapeutic and preventive approaches.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Identification and Validation of RNA Modification-Related Biomarkers in Dilated cardiomyopathy\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-12-17 03:45:17\",\"doi\":\"10.21203/rs.3.rs-8221884/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"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\":\"d7d43d03-f6ec-4465-a281-615987bb2d78\",\"owner\":[],\"postedDate\":\"December 17th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[{\"id\":59761775,\"name\":\"Health sciences/Biomarkers\"},{\"id\":59761776,\"name\":\"Health sciences/Cardiology\"},{\"id\":59761777,\"name\":\"Biological sciences/Computational biology and bioinformatics\"},{\"id\":59761778,\"name\":\"Health sciences/Diseases\"}],\"tags\":[],\"updatedAt\":\"2026-02-18T19:54:20+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-12-17 03:45:17\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-8221884\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-8221884\",\"identity\":\"rs-8221884\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}