Shared Molecular Features Between Primary Biliary Cholangitis and Hepatocellular Carcinoma Define a Prognostic Gene Signature for Risk Stratification

Shared Molecular Features Between Primary Biliary Cholangitis and Hepatocellular Carcinoma Define a Prognostic Gene Signature for Risk Stratification | 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 Shared Molecular Features Between Primary Biliary Cholangitis and Hepatocellular Carcinoma Define a Prognostic Gene Signature for Risk Stratification Yuexin Luo, Hongchun Luo This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9183430/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 Primary Biliary Cholangitis (PBC) is an autoimmune liver disease that may progress to Hepatocellular Carcinoma (HCC) in a subset of patients. However, the molecular features shared between PBC and HCC remain largely unknown. This study aimed to identify common genes linking these diseases and to develop a prognostic model for HCC, with comprehensive analyses to support risk stratification and clinical decision-making. Methods Transcriptomic datasets from public repositories were integrated. Differential expression analysis, WGCNA, and survival analyses were conducted to identify the genes shared between PBC and HCC. Peripheral blood samples from patients with HCC and PBC were collected to validate the expression of key genes using RT-qPCR. A risk score (RS) model was constructed using LASSO regression and validated in an independent cohort. A nomogram combining RS and clinical variables was developed. Mutation profiles, immune infiltration, drug sensitivity, immunotherapy response, and pathway enrichment were systematically analyzed. Results Seven genes (MARCH1, ARHGAP4, MZB1, PLCH2, MMP9, SLC16A3, and ZNF341) were included in the RS model. RT-qPCR confirmed significant differential expression of these genes in peripheral blood samples, consistent with the transcriptomic results. The RS model demonstrated robust prognostic value in both the training and validation cohorts, and the nomogram exhibited strong predictive performance. Comparative analyses between the high- and low-risk groups revealed distinct immune cell compositions, mutation landscapes, drug sensitivity profiles, immunotherapy responsiveness, and pathway activities. Conclusions The seven-gene RS model and nomogram effectively stratified prognostic risk in PBC-associated HCC and highlighted potential molecular connections between these diseases, offering insights for personalized prognosis and therapeutic strategies. Primary Biliary Cholangitis Hepatocellular Carcinoma Prognostic Risk Model Differentially Expressed Genes Full Text Additional Declarations No competing interests reported. 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-9183430","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":616848673,"identity":"f9512ae1-1994-4b03-a6c9-34afd93affb0","order_by":0,"name":"Yuexin Luo","email":"","orcid":"","institution":"The First Affiliated Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yuexin","middleName":"","lastName":"Luo","suffix":""},{"id":616848674,"identity":"7b2202ca-18d7-4657-8951-f0f64159f5f3","order_by":1,"name":"Hongchun Luo","email":"data:image/png;base64,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","orcid":"","institution":"The First Affiliated Hospital of Chongqing Medical University","correspondingAuthor":true,"prefix":"","firstName":"Hongchun","middleName":"","lastName":"Luo","suffix":""}],"badges":[],"createdAt":"2026-03-21 05:53:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9183430/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9183430/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108192780,"identity":"14c34330-ce70-4279-a428-4cb502e4feac","added_by":"auto","created_at":"2026-04-30 10:12:04","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1676870,"visible":true,"origin":"","legend":"","description":"","filename":"Article.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9183430/v1_covered_1250f493-9b4d-4b1c-aa40-d8aa7cb61c86.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eShared Molecular Features Between Primary Biliary Cholangitis and Hepatocellular Carcinoma Define a Prognostic Gene Signature for Risk Stratification\u003c/p\u003e","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":"Primary Biliary Cholangitis, Hepatocellular Carcinoma, Prognostic Risk Model, Differentially Expressed Genes","lastPublishedDoi":"10.21203/rs.3.rs-9183430/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9183430/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePrimary Biliary Cholangitis (PBC) is an autoimmune liver disease that may progress to Hepatocellular Carcinoma (HCC) in a subset of patients. However, the molecular features shared between PBC and HCC remain largely unknown. This study aimed to identify common genes linking these diseases and to develop a prognostic model for HCC, with comprehensive analyses to support risk stratification and clinical decision-making.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eTranscriptomic datasets from public repositories were integrated. Differential expression analysis, WGCNA, and survival analyses were conducted to identify the genes shared between PBC and HCC. Peripheral blood samples from patients with HCC and PBC were collected to validate the expression of key genes using RT-qPCR. A risk score (RS) model was constructed using LASSO regression and validated in an independent cohort. A nomogram combining RS and clinical variables was developed. Mutation profiles, immune infiltration, drug sensitivity, immunotherapy response, and pathway enrichment were systematically analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSeven genes (MARCH1, ARHGAP4, MZB1, PLCH2, MMP9, SLC16A3, and ZNF341) were included in the RS model. RT-qPCR confirmed significant differential expression of these genes in peripheral blood samples, consistent with the transcriptomic results. The RS model demonstrated robust prognostic value in both the training and validation cohorts, and the nomogram exhibited strong predictive performance. Comparative analyses between the high- and low-risk groups revealed distinct immune cell compositions, mutation landscapes, drug sensitivity profiles, immunotherapy responsiveness, and pathway activities.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe seven-gene RS model and nomogram effectively stratified prognostic risk in PBC-associated HCC and highlighted potential molecular connections between these diseases, offering insights for personalized prognosis and therapeutic strategies.\u003c/p\u003e","manuscriptTitle":"Shared Molecular Features Between Primary Biliary Cholangitis and Hepatocellular Carcinoma Define a Prognostic Gene Signature for Risk Stratification","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-06 09:00:51","doi":"10.21203/rs.3.rs-9183430/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":"22ecc560-9550-4776-8c59-4606ff5eb6bb","owner":[],"postedDate":"April 6th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Rejected","date":"2026-04-30T09:53:39+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"269746589305081503376260486243380895840","date":"2026-04-30T06:01:11+00:00","index":73,"fulltext":""},{"type":"reviewerAgreed","content":"202104191560841115398457467384260769385","date":"2026-04-29T16:30:32+00:00","index":72,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-29T07:44:49+00:00","index":69,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-30T10:11:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-06 09:00:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9183430","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9183430","identity":"rs-9183430","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}