A Novel Therapeutic Strategy for Cervical Cancer: Research on Novel Biomarkers Associated with Mitophagy and Pyroptosis and Their Targeted Drug Development

A Novel Therapeutic Strategy for Cervical Cancer: Research on Novel Biomarkers Associated with Mitophagy and Pyroptosis and Their Targeted Drug Development | 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 A Novel Therapeutic Strategy for Cervical Cancer: Research on Novel Biomarkers Associated with Mitophagy and Pyroptosis and Their Targeted Drug Development Junda Ren, Shuxian Zhao, Xiyang Xu, Xiangjun Chen, Xin Li, Lei Shen, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9263470/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 13 You are reading this latest preprint version Abstract Background: Mitophagy and pyroptosis exert intricate regulatory interactions in cellular physiological and pathological processes, yet their functional significance and clinical implications in cervical cancer remain incompletely elucidated. This study was designed to investigate whether these two biological processes and their associated genes can serve as reliable targets for the prediction, prevention, and personalized treatment of cervical cancer. Methods: Differentially expressed genes related to mitophagy and pyroptosis were initially screened using weighted gene co-expression network analysis and differential gene expression analysis, followed by machine learning-based identification of characteristic genes. Integrated bioinformatics analyses, including pathway enrichment, Gene Ontology annotation, survival correlation analysis, immune infiltration evaluation, and single-cell sequencing analysis, were performed. A competing endogenous RNA regulatory network was constructed. The OncoPredict R package was utilized to predict potential small-molecule therapeutic agents, with the binding stability of candidate drugs to target genes verified via molecular docking and molecular dynamics simulations. Results: The mitophagy-related gene DCN and pyroptosis-related genes TACR1, KIF23, and MEG3 exhibited significant diagnostic and prognostic predictive value in cervical cancer. Pseudotime trajectory analysis revealed dynamic expression fluctuations of DCN and MEG3 during disease progression, while KIF23 and TACR1 maintained relatively stable expression patterns. Cell-cell communication analysis demonstrated active crosstalk among multiple cell populations within cervical cancer lesions. Doxorubicin was identified as a promising therapeutic candidate, showing stable binding affinity to DCN, TACR1, and KIF23, and its therapeutic effects may be mediated through the regulation of mitophagy and pyroptosis signaling pathways. Conclusion: Mitophagy and pyroptosis synergistically drive the progression of cervical cancer. The four identified key genes possess robust prognostic utility, and doxorubicin exhibits considerable potential for personalized cervical cancer therapy by targeting these genes, thereby providing novel theoretical basis and clinical insights for the precise treatment of cervical cancer. Biological sciences/Cancer Biological sciences/Computational biology and bioinformatics Health sciences/Oncology Cervical Cancer Mitophagy Pyroptosis Targeted drug development Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 17 May, 2026 Reviews received at journal 14 May, 2026 Reviewers agreed at journal 14 May, 2026 Reviewers agreed at journal 13 May, 2026 Reviewers agreed at journal 13 May, 2026 Reviews received at journal 12 May, 2026 Reviewers agreed at journal 20 Apr, 2026 Reviewers agreed at journal 18 Apr, 2026 Reviewers invited by journal 06 Apr, 2026 Editor invited by journal 02 Apr, 2026 Editor assigned by journal 31 Mar, 2026 Submission checks completed at journal 31 Mar, 2026 First submitted to journal 30 Mar, 2026 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. 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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-9263470","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":618639446,"identity":"dbe84375-0fb0-42ef-9be5-c45c19f12010","order_by":0,"name":"Junda Ren","email":"","orcid":"","institution":"Qiqihar Medical University","correspondingAuthor":false,"prefix":"","firstName":"Junda","middleName":"","lastName":"Ren","suffix":""},{"id":618639447,"identity":"49527242-af18-4713-ae66-ee39f4bd08c4","order_by":1,"name":"Shuxian Zhao","email":"","orcid":"","institution":"Qiqihar Medical 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Pyroptosis, Targeted drug development","lastPublishedDoi":"10.21203/rs.3.rs-9263470/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9263470/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Mitophagy and pyroptosis exert intricate regulatory interactions in cellular physiological and pathological processes, yet their functional significance and clinical implications in cervical cancer remain incompletely elucidated. This study was designed to investigate whether these two biological processes and their associated genes can serve as reliable targets for the prediction, prevention, and personalized treatment of cervical cancer.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Differentially expressed genes related to mitophagy and pyroptosis were initially screened using weighted gene co-expression network analysis and differential gene expression analysis, followed by machine learning-based identification of characteristic genes. Integrated bioinformatics analyses, including pathway enrichment, Gene Ontology annotation, survival correlation analysis, immune infiltration evaluation, and single-cell sequencing analysis, were performed. A competing endogenous RNA regulatory network was constructed. The OncoPredict R package was utilized to predict potential small-molecule therapeutic agents, with the binding stability of candidate drugs to target genes verified via molecular docking and molecular dynamics simulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe mitophagy-related gene DCN and pyroptosis-related genes TACR1, KIF23, and MEG3 exhibited significant diagnostic and prognostic predictive value in cervical cancer. Pseudotime trajectory analysis revealed dynamic expression fluctuations of DCN and MEG3 during disease progression, while KIF23 and TACR1 maintained relatively stable expression patterns. Cell-cell communication analysis demonstrated active crosstalk among multiple cell populations within cervical cancer lesions. Doxorubicin was identified as a promising therapeutic candidate, showing stable binding affinity to DCN, TACR1, and KIF23, and its therapeutic effects may be mediated through the regulation of mitophagy and pyroptosis signaling pathways.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Mitophagy and pyroptosis synergistically drive the progression of cervical cancer. The four identified key genes possess robust prognostic utility, and doxorubicin exhibits considerable potential for personalized cervical cancer therapy by targeting these genes, thereby providing novel theoretical basis and clinical insights for the precise treatment of cervical cancer.\u003c/p\u003e","manuscriptTitle":"A Novel Therapeutic Strategy for Cervical Cancer: Research on Novel Biomarkers Associated with Mitophagy and Pyroptosis and Their Targeted Drug Development","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-13 02:27:31","doi":"10.21203/rs.3.rs-9263470/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"40467869267895478681883295614110503630","date":"2026-05-17T12:24:53+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-14T09:55:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"25786316654711400293373122410214466501","date":"2026-05-14T09:29:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"267108457616401297442593744643710277145","date":"2026-05-13T16:59:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"307360822667980316680824803478507521920","date":"2026-05-13T11:29:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-12T07:08:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"211234485860414190650870997749373556371","date":"2026-04-20T04:32:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"316544075063352733486701966794953563626","date":"2026-04-18T09:21:18+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-07T03:16:06+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-02T10:04:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-31T05:19:17+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-31T05:18:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-03-30T07:02:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"92f88a05-2a7b-4197-9d91-b2d76e85a352","owner":[],"postedDate":"April 13th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"40467869267895478681883295614110503630","date":"2026-05-17T12:24:53+00:00","index":211,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-14T09:55:49+00:00","index":210,"fulltext":""},{"type":"reviewerAgreed","content":"25786316654711400293373122410214466501","date":"2026-05-14T09:29:45+00:00","index":209,"fulltext":""},{"type":"reviewerAgreed","content":"267108457616401297442593744643710277145","date":"2026-05-13T16:59:31+00:00","index":208,"fulltext":""},{"type":"reviewerAgreed","content":"307360822667980316680824803478507521920","date":"2026-05-13T11:29:27+00:00","index":207,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-12T07:08:23+00:00","index":165,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":65825007,"name":"Biological sciences/Cancer"},{"id":65825008,"name":"Biological sciences/Computational biology and bioinformatics"},{"id":65825009,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2026-04-13T02:27:32+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-13 02:27:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9263470","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9263470","identity":"rs-9263470","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}