Scene: Inferring subtype-specific ceRNA modules in breast cancer

Scene: Inferring subtype-specific ceRNA modules in breast cancer | 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 Scene: Inferring subtype-specific ceRNA modules in breast cancer Haolin Yang, Qian Lu, Jiaxin Wang, Junpeng Zhu, Yu Jiang, Qi Zhang, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7181552/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background The heterogeneity of breast cancer poses a fundamental challenge to clinical management, manifesting both in molecular subtype diversity and functionally distinct gene modules. Long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) or microRNA (miRNA) sponges are emerging biomarkers of breast cancer. Accurate identification of subtype-specific ceRNA modules could contribute to precision medicine in breast cancer. Results In this work, we propose a novel framework Scene (Subtype-specific ceRNA modules) to infer lncRNA-related breast cancer subtype-specific ceRNA modules from heterogeneous data, including gene expression data and priori information of miRNA targets. For five breast cancer subtypes, most of ceRNA modules tend to be unique. Across 22 breast cancer-specific ceRNA modules, 20 ceRNA modules are significantly enriched in various biological processes or pathways, indicating that these modules play distinct biological functions in different subtypes. Survival analysis further indicates that all identified ceRNA modules serve as potential prognostic biomarkers capable of discriminating between high- and low-risk breast cancer groups. Moreover, classification analysis shows that all inferred ceRNA modules function as potential diagnostic biomarkers for distinguishing breast cancer subtypes. Finally, immune infiltration analysis reveals that all identified ceRNA modules show significant correlation with one or more immune cell types, suggesting their potential involvement in immune regulation within the tumor microenvironment. Conclusions This study provides a new perspective for investigating the molecular mechanism of breast cancer subtypes, and lays a theoretical foundation for the development of breast cancer subtype-specific biomarkers. ceRNA miRNA lncRNA ceRNA module breast cancer Full Text Additional Declarations No competing interests reported. Supplementary Files Additionalfile1.xlsx Additional file 1 – Markers of 24 immune cell types. The 24 immune cell types include aDCs, iDCs, pDC, DCs, B cells, T cells, CD8+ T cells, T helper cells, Th1 cells, Th2 cells, Th17 cells, Tcm, Tem, Tfh, Tgd, Treg cells, NKs, NK CD56bright cells, NK CD56dim cells, Macrophages, Neutrophils, Mast cells, Eosinophils, and cytotoxic cells. Additionalfile2.xlsx Additional file 2 – Functional enrichment analysis of Normal-, LumA-, Her2-, LumB- and Basal- specific ceRNA module. The significantly enriched terms include BP, KEGG and Reactome terms. Additionalfile3.xlsx Additional file 3 – Disease enrichment analysis of Normal-, LumA-, Her2-, LumB- and Basal- specific ceRNA modules. The significantly enriched terms contain HDO, DisGeNET and NCG terms. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 25 Aug, 2025 Editor invited by journal 23 Jul, 2025 Editor assigned by journal 23 Jul, 2025 Submission checks completed at journal 23 Jul, 2025 First submitted to journal 21 Jul, 2025 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-7181552","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":488936115,"identity":"02598bb8-773f-4b49-819a-493adb622a8c","order_by":0,"name":"Haolin Yang","email":"","orcid":"","institution":"Dali University","correspondingAuthor":false,"prefix":"","firstName":"Haolin","middleName":"","lastName":"Yang","suffix":""},{"id":488936116,"identity":"0ac743ec-ca8f-4819-b77a-e8015879de07","order_by":1,"name":"Qian Lu","email":"","orcid":"","institution":"Dali University","correspondingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"Lu","suffix":""},{"id":488936117,"identity":"40c3a7f5-1de8-43fe-871f-cbc9ba33bd86","order_by":2,"name":"Jiaxin Wang","email":"","orcid":"","institution":"Dali University","correspondingAuthor":false,"prefix":"","firstName":"Jiaxin","middleName":"","lastName":"Wang","suffix":""},{"id":488936118,"identity":"e3b32796-90d0-4ddc-89d7-8fb955d66aa8","order_by":3,"name":"Junpeng Zhu","email":"","orcid":"","institution":"Dali University","correspondingAuthor":false,"prefix":"","firstName":"Junpeng","middleName":"","lastName":"Zhu","suffix":""},{"id":488936119,"identity":"fdaf68fe-d42a-4203-972b-2fb4dacc2b64","order_by":4,"name":"Yu Jiang","email":"","orcid":"","institution":"Dali University","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Jiang","suffix":""},{"id":488936120,"identity":"7cb466da-4beb-4975-acba-84b55327299c","order_by":5,"name":"Qi Zhang","email":"","orcid":"","institution":"Dali University","correspondingAuthor":false,"prefix":"","firstName":"Qi","middleName":"","lastName":"Zhang","suffix":""},{"id":488936121,"identity":"076e4a45-b3c9-41ba-9d67-66496aac0ad4","order_by":6,"name":"Jian Gao","email":"","orcid":"","institution":"Dali University","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Gao","suffix":""},{"id":488936122,"identity":"0b682288-42d3-428d-b27b-a7a708a256be","order_by":7,"name":"Chunwen Zhao","email":"","orcid":"","institution":"Dali University","correspondingAuthor":false,"prefix":"","firstName":"Chunwen","middleName":"","lastName":"Zhao","suffix":""},{"id":488936123,"identity":"3c2bd853-0079-418d-9e63-6da76724d60f","order_by":8,"name":"Xuemei Wei","email":"","orcid":"","institution":"Dali University","correspondingAuthor":false,"prefix":"","firstName":"Xuemei","middleName":"","lastName":"Wei","suffix":""},{"id":488936124,"identity":"24ded273-5320-49e3-9f99-83f35dd0eba8","order_by":9,"name":"Junpeng Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvElEQVRIiWNgGAWjYFCCA4wPeBgseIAsA6K1MBvwMEiQpIWBDahegoF4LfKNZ49VvKmRkGFgb94mwVBzh7AWxoZzaTfnHANaxHOsTILh2DPCWpgZzpjd5gG7LcdMgrHhMGEtbEAtxTz/gFrk3xCphQeohZm3DWQLD5FaJBjOJUvO7ZPgYeNJK7ZIOEaEFvkZZw9+ePPNxp6f/fDGGx9qiNDCIHEGQrOBiAQiNDAw8PcQpWwUjIJRMApGMgAAVKMwsxQr44kAAAAASUVORK5CYII=","orcid":"","institution":"Dali University","correspondingAuthor":true,"prefix":"","firstName":"Junpeng","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-07-22 01:53:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7181552/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7181552/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87364019,"identity":"0926b018-563a-4f5f-addb-ee0a845c4aea","added_by":"auto","created_at":"2025-07-23 06:09:57","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1368926,"visible":true,"origin":"","legend":"","description":"","filename":"Scene.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7181552/v1_covered_ce2a7c89-a666-4117-aa3f-dfd289060533.pdf"},{"id":87358878,"identity":"b8764288-db98-4a6f-9e08-a8eccd7958f3","added_by":"auto","created_at":"2025-07-23 05:37:58","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":50932,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 1 – Markers of 24 immune cell types. The 24 immune cell types include aDCs, iDCs, pDC, DCs, B cells, T cells, CD8+ T cells, T helper cells, Th1 cells, Th2 cells, Th17 cells, Tcm, Tem, Tfh, Tgd, Treg cells, NKs, NK CD56bright cells, NK CD56dim cells, Macrophages, Neutrophils, Mast cells, Eosinophils, and cytotoxic cells.\u003c/p\u003e","description":"","filename":"Additionalfile1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7181552/v1/af982a3e22cae5a12aeb709e.xlsx"},{"id":87360249,"identity":"301cb84b-a7cc-42fb-ab9c-1aa4cdf6a602","added_by":"auto","created_at":"2025-07-23 05:45:56","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":616778,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 2 – Functional enrichment analysis of Normal-, LumA-, Her2-, LumB- and Basal- specific ceRNA module. The significantly enriched terms include BP, KEGG and Reactome terms.\u003c/p\u003e","description":"","filename":"Additionalfile2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7181552/v1/4a9786d7d278d3c9903f0b36.xlsx"},{"id":87358787,"identity":"b576cd64-be83-4703-9d02-151f205c322d","added_by":"auto","created_at":"2025-07-23 05:37:55","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":1025836,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 3 – Disease enrichment analysis of Normal-, LumA-, Her2-, LumB- and Basal- specific ceRNA modules. 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Long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) or microRNA (miRNA) sponges are emerging biomarkers of breast cancer. Accurate identification of subtype-specific ceRNA modules could contribute to precision medicine in breast cancer.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eIn this work, we propose a novel framework Scene (Subtype-specific ceRNA modules) to infer lncRNA-related breast cancer subtype-specific ceRNA modules from heterogeneous data, including gene expression data and priori information of miRNA targets. For five breast cancer subtypes, most of ceRNA modules tend to be unique. Across 22 breast cancer-specific ceRNA modules, 20 ceRNA modules are significantly enriched in various biological processes or pathways, indicating that these modules play distinct biological functions in different subtypes. Survival analysis further indicates that all identified ceRNA modules serve as potential prognostic biomarkers capable of discriminating between high- and low-risk breast cancer groups. Moreover, classification analysis shows that all inferred ceRNA modules function as potential diagnostic biomarkers for distinguishing breast cancer subtypes. Finally, immune infiltration analysis reveals that all identified ceRNA modules show significant correlation with one or more immune cell types, suggesting their potential involvement in immune regulation within the tumor microenvironment.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThis study provides a new perspective for investigating the molecular mechanism of breast cancer subtypes, and lays a theoretical foundation for the development of breast cancer subtype-specific biomarkers.\u003c/p\u003e","manuscriptTitle":"Scene: Inferring subtype-specific ceRNA modules in breast cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-23 05:37:49","doi":"10.21203/rs.3.rs-7181552/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2025-08-25T16:43:58+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-23T09:09:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-23T08:53:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-23T08:51:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2025-07-22T01:42:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f62d4212-0c94-4bf7-957d-c7dc3117230c","owner":[],"postedDate":"July 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-08-25T16:53:18+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-23 05:37:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7181552","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7181552","identity":"rs-7181552","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}