Two Previously Unreported Prostate Cancer Gene Candidates Identified Through Governed Multi-Omics Screening of TCGA-PRAD

Two Previously Unreported Prostate Cancer Gene Candidates Identified Through Governed Multi-Omics Screening of TCGA-PRAD | 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 Two Previously Unreported Prostate Cancer Gene Candidates Identified Through Governed Multi-Omics Screening of TCGA-PRAD George Soto This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9383327/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 Most published TCGA-PRAD analyses report a short list of differentially expressed genes selected by a single statistical metric. Here we describe a governed multi-omics screening pipeline that filters all 19,010 genes in the TCGA-PRAD cohort through four independent and non-compensating quality gates: statistical significance, cross-validation reproducibility, bootstrap sign consistency, and data completeness. Of 19,010 genes, 942 (5.0%) passed all four gates. Ten of these matched established prostate cancer genes in COSMIC and the published literature, confirming the pipeline's sensitivity. Cross-referencing the remaining 932 against PubMed identified two genes with no prior prostate cancer association: DNAH5 (Dynein Axonemal Heavy Chain 5), an axonemal dynein motor protein with 35 publications in other cancer contexts but none in prostate, showing 4.4-fold overexpression (adj. p = 1.22x10^-17); and PRR36 (Proline Rich 36), a gene with no publications in any cancer context, showing 3.7-fold overexpression (adj. p = 2.57x10^-21). Both top candidates replicate with the same direction and significance in the independent MSKCC cohort (GSE21034). A targeted PubMed audit of seven canonical axonemal dynein and ciliary motor genes (DNAI1, DNAI2, DNALI1, NME8, DNAL1, CCDC114, RSPH4A) returned zero prostate cancer publications for any of them, indicating that this protein family is essentially unstudied in the prostate context. Notably, DNAH5 is overexpressed while all 10 of its high-confidence STRING partners (scores 0.935-0.997), all axonemal/ciliary components, are absent from our 942-gene candidate set -- a pattern inconsistent with coordinated dysregulation of the canonical ciliary program. These results demonstrate that multi-evidence gating with strict non-compensation can identify reproducible candidates overlooked by conventional single-metric screens, and surface biological patterns -- such as isolated overexpression decoupled from a gene's known interactome -- that warrant mechanistic follow-up. Biochemical Research Methods Prostate cancer multi-omics cancer genomics gene expression DNAH5 biomarker discovery Full Text Additional Declarations The authors declare no competing interests. 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-9383327","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":621207045,"identity":"88bd65fe-3edd-46e7-b4a0-8192c1fa2acb","order_by":0,"name":"George Soto","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIiWNgGAWjYHAD5gMMCQzMJGjgYWBLgGhhI14LjwHIKsJa5N2bj338UlEnZ8/e83XDwx3WefzyzRsYflRsw6nF8Myx5NkyZw4b8/Cc3XYj8Ux6sWQbWwFjz5nbuLXMyDFmlmw7kNgjkQvU0nY4ccMxHgNmxjY8Wua/AWr5VwfUkvMMrGU/IS3yEjzGjB8bmEFa2CC2sBHQYsCTlszMcAzolzPHzIBa0hNnHEsrOIjPL/Lthw8z/qipk2Nvb35282ebdWJ/8+GND35U4LHlADAueLAI4gbyDQwMjD/QteDTMQpGwSgYBSMPAAB/bFnjq9bYjgAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0009-0004-2394-4562","institution":"Infinity Software Architects, Inc.","correspondingAuthor":true,"prefix":"","firstName":"George","middleName":"","lastName":"Soto","suffix":""}],"badges":[],"createdAt":"2026-04-10 22:45:33","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-9383327/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9383327/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106961067,"identity":"c12ff755-5679-42d2-8d9f-92875352ddd9","added_by":"auto","created_at":"2026-04-15 09:24:08","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":433762,"visible":true,"origin":"","legend":"","description":"","filename":"prostatecandidatespreprintresearchv3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9383327/v1_covered_19636af6-65c6-462b-9cdc-033ef18e97ed.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eTwo Previously Unreported Prostate Cancer Gene Candidates Identified Through Governed Multi-Omics Screening of TCGA-PRAD\u003c/strong\u003e\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Infinity Software Architects, Inc.","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":"Prostate cancer, multi-omics, cancer genomics, gene expression, DNAH5, biomarker discovery","lastPublishedDoi":"10.21203/rs.3.rs-9383327/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9383327/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMost published TCGA-PRAD analyses report a short list of differentially expressed genes selected by a\u003c/p\u003e\n\u003cp\u003esingle statistical metric. Here we describe a governed multi-omics screening pipeline that filters all 19,010\u003c/p\u003e\n\u003cp\u003egenes in the TCGA-PRAD cohort through four independent and non-compensating quality gates: statistical\u003c/p\u003e\n\u003cp\u003esignificance, cross-validation reproducibility, bootstrap sign consistency, and data completeness. Of\u003c/p\u003e\n\u003cp\u003e19,010 genes, 942 (5.0%) passed all four gates. Ten of these matched established prostate cancer genes in\u003c/p\u003e\n\u003cp\u003eCOSMIC and the published literature, confirming the pipeline's sensitivity. Cross-referencing the\u003c/p\u003e\n\u003cp\u003eremaining 932 against PubMed identified two genes with no prior prostate cancer association: DNAH5\u003c/p\u003e\n\u003cp\u003e(Dynein Axonemal Heavy Chain 5), an axonemal dynein motor protein with 35 publications in other cancer\u003c/p\u003e\n\u003cp\u003econtexts but none in prostate, showing 4.4-fold overexpression (adj. p = 1.22x10^-17); and PRR36 (Proline\u003c/p\u003e\n\u003cp\u003eRich 36), a gene with no publications in any cancer context, showing 3.7-fold overexpression (adj. p =\u003c/p\u003e\n\u003cp\u003e2.57x10^-21). Both top candidates replicate with the same direction and significance in the independent\u003c/p\u003e\n\u003cp\u003eMSKCC cohort (GSE21034). A targeted PubMed audit of seven canonical axonemal dynein and ciliary\u003c/p\u003e\n\u003cp\u003emotor genes (DNAI1, DNAI2, DNALI1, NME8, DNAL1, CCDC114, RSPH4A) returned zero prostate cancer\u003c/p\u003e\n\u003cp\u003epublications for any of them, indicating that this protein family is essentially unstudied in the prostate\u003c/p\u003e\n\u003cp\u003econtext. Notably, DNAH5 is overexpressed while all 10 of its high-confidence STRING partners (scores\u003c/p\u003e\n\u003cp\u003e0.935-0.997), all axonemal/ciliary components, are absent from our 942-gene candidate set -- a pattern\u003c/p\u003e\n\u003cp\u003einconsistent with coordinated dysregulation of the canonical ciliary program. These results demonstrate\u003c/p\u003e\n\u003cp\u003ethat multi-evidence gating with strict non-compensation can identify reproducible candidates overlooked\u003c/p\u003e\n\u003cp\u003eby conventional single-metric screens, and surface biological patterns -- such as isolated overexpression\u003c/p\u003e\n\u003cp\u003edecoupled from a gene's known interactome -- that warrant mechanistic follow-up.\u003c/p\u003e","manuscriptTitle":"Two Previously Unreported Prostate Cancer Gene Candidates Identified Through Governed Multi-Omics Screening of TCGA-PRAD","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-14 17:17:42","doi":"10.21203/rs.3.rs-9383327/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":"a0ddd610-bf73-4b47-85e5-37f5c67db7a8","owner":[],"postedDate":"April 14th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":66315376,"name":"Biochemical Research Methods"}],"tags":[],"updatedAt":"2026-04-14T17:17:42+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-14 17:17:42","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9383327","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9383327","identity":"rs-9383327","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}