Exosomal MicroRNA from Blood Plasma as a Predictive Biomarker for Bleeding Tendency in Dengue Infection

Exosomal MicroRNA from Blood Plasma as a Predictive Biomarker for Bleeding Tendency in Dengue Infection | 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 Exosomal MicroRNA from Blood Plasma as a Predictive Biomarker for Bleeding Tendency in Dengue Infection Gokulakannan Venkatesan, Wan Suriana Wan Ab Rahman, Wan Nazatul Shima Shahidan, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7974237/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 Purpose Dengue can manifest as a mild febrile illness to life-threatening haemorrhagic fever. There are currently no predictive markers for individuals prone to bleeding. Therefore, this study aims to investigate the capability of exosomal plasma microRNA (miRNA) expression as a biomarker for bleeding tendency. Methods Microarray was used to profile the miRNAs from plasma exosomes of dengue patients with and without warning sign to find potential biomarkers for bleeding tendency. Predicted target genes were identified using a bioinformatic software and database. miRNA–mRNA interaction network was constructed to identify hub genes. The expression level of miRNAs was validated using RT-qPCR, and its diagnostic performance was assessed using the ROC curve. Finally, functional enrichment pathway analysis, gene ontology and co-expression analysis were performed. Results Microarray profiling revealed 24 upregulated miRNAs with a fold change cut-off value of log2 ≥ 2.0 in the plasma of dengue patients with warning signs compared to those without. Of the upregulated miRNAs, hsa-miR-107 and hsa-miR-6879-5p miRNAs were identified as reliable candidates in predicting bleeding tendency. In silico functional analysis of predicted target genes of these miRNAs suggested their involvement in bleeding manifestation. RT-qPCR analysis showed hsa-miR-107 and hsa-miR-6879-5p were markedly upregulated in dengue patients with warning signs. ROC analysis indicated strong diagnostic potential, and target gene analysis indicated their involvement in platelet dysfunction and vascular processes linked to disease severity. Conclusion This study highlights hsa-miR-107 and hsa-miR-6879-5p expression as promising biomarkers in predicting dengue progression. Further studies could pave the way for improved diagnostic strategies. Health sciences/Biomarkers Biological sciences/Computational biology and bioinformatics Health sciences/Diseases Biological sciences/Genetics Biological sciences/Molecular biology biomarker dengue bleeding manifestations profiling miRNA exosomes Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementry.docx 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-7974237","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":545883861,"identity":"beb26889-e947-4a44-83c3-e8bf449128ed","order_by":0,"name":"Gokulakannan Venkatesan","email":"","orcid":"","institution":"School of Dental Sciences, Universiti Sains Malaysia","correspondingAuthor":false,"prefix":"","firstName":"Gokulakannan","middleName":"","lastName":"Venkatesan","suffix":""},{"id":545883862,"identity":"4323b177-32ca-4e76-b760-75af40eb0f40","order_by":1,"name":"Wan Suriana Wan Ab 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Infection","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":"biomarker, dengue, bleeding manifestations, profiling, miRNA, exosomes","lastPublishedDoi":"10.21203/rs.3.rs-7974237/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7974237/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eDengue can manifest as a mild febrile illness to life-threatening haemorrhagic fever. There are currently no predictive markers for individuals prone to bleeding. Therefore, this study aims to investigate the capability of exosomal plasma microRNA (miRNA) expression as a biomarker for bleeding tendency.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eMicroarray was used to profile the miRNAs from plasma exosomes of dengue patients with and without warning sign to find potential biomarkers for bleeding tendency. Predicted target genes were identified using a bioinformatic software and database. miRNA\u0026ndash;mRNA interaction network was constructed to identify hub genes. The expression level of miRNAs was validated using RT-qPCR, and its diagnostic performance was assessed using the ROC curve. Finally, functional enrichment pathway analysis, gene ontology and co-expression analysis were performed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eMicroarray profiling revealed 24 upregulated miRNAs with a fold change cut-off value of log2\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;2.0 in the plasma of dengue patients with warning signs compared to those without. Of the upregulated miRNAs, hsa-miR-107 and hsa-miR-6879-5p miRNAs were identified as reliable candidates in predicting bleeding tendency. In silico functional analysis of predicted target genes of these miRNAs suggested their involvement in bleeding manifestation. RT-qPCR analysis showed hsa-miR-107 and hsa-miR-6879-5p were markedly upregulated in dengue patients with warning signs. ROC analysis indicated strong diagnostic potential, and target gene analysis indicated their involvement in platelet dysfunction and vascular processes linked to disease severity.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThis study highlights hsa-miR-107 and hsa-miR-6879-5p expression as promising biomarkers in predicting dengue progression. Further studies could pave the way for improved diagnostic strategies.\u003c/p\u003e","manuscriptTitle":"Exosomal MicroRNA from Blood Plasma as a Predictive Biomarker for Bleeding Tendency in Dengue Infection","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-18 19:49:08","doi":"10.21203/rs.3.rs-7974237/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":"6535491c-eb2b-4a22-b82f-f74c5b140128","owner":[],"postedDate":"November 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":58072875,"name":"Health sciences/Biomarkers"},{"id":58072876,"name":"Biological sciences/Computational biology and bioinformatics"},{"id":58072877,"name":"Health sciences/Diseases"},{"id":58072878,"name":"Biological sciences/Genetics"},{"id":58072879,"name":"Biological sciences/Molecular biology"}],"tags":[],"updatedAt":"2026-03-23T07:58:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-18 19:49:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7974237","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7974237","identity":"rs-7974237","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}