Comparative Transcriptomic Analysis of Pathogenic Mechanisms in Papillary Thyroid Carcinoma and Hashimoto's Thyroiditis

Comparative Transcriptomic Analysis of Pathogenic Mechanisms in Papillary Thyroid Carcinoma and Hashimoto's Thyroiditis | 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 Comparative Transcriptomic Analysis of Pathogenic Mechanisms in Papillary Thyroid Carcinoma and Hashimoto's Thyroiditis Xuelu Xu, Yuqing Ma, Weibin Fan, Wenxia Wang, Zhizheng Xu, Jie Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6689784/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 Papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT) are diseases where one is a "cancer" that has escaped immune system surveillance, and the other is an "autoimmune disease" that attacks the body's own systems. They appear to be antagonistic in form, but in reality, they can occur simultaneously. The similarities or differences in their gene molecular expression are worth in-depth discussion. Research Methods This study searched the GEO database, integrating 4 GEO datasets to compare the gene expression similarities and differences in thyroid tissues of papillary thyroid carcinoma (PTC), Hashimoto's thyroiditis (HT), and concurrent PTC and HT (PTC_HT) against normal tissue (Control). The limma software package was used to select differentially expressed genes compared to normal tissue (Control), followed by KEGG clustering and gene pathway interaction analysis. Finally, we verified the differentially expressed genes discovered in our collected PTC, HT, and adjacent cancer tissues. Results We integrated and analyzed gene expression data from 166 tissue samples in the database, finding 202 genes with significant expression differences in PTC, HT, and PTC_HT pathological phenotypes. Moreover, these 202 genes showed consistent expression trends (i.e., same direction of increase or decrease) in the cells of the three pathological phenotypes. They are mainly inflammatory and chemokine factors (CXCL8, CXCL9, CXCL10, and IL8), with thyroid cells in all three diseases existing in an environment where chemokines activate inflammation. They also do not respond to p53 and FAS-induced apoptosis signals. Comparing genes with completely opposite expression trends between PTC and HT, we found these genes mainly concentrated in the ECM-receptor interaction pathway, involving genes such as FN1, LAMB1, and LAMC1. By combining DEGs and hubGenes, we found that differences in the FN1-DUSP6-ETV5-NFATC1/3 signaling axis may be the cause of different phenotypes in HT and PTC. QPCR and WB verification of collected PTC, HT, and adjacent cancer patient tissues also supported these findings. Conclusion Based on the above results, we believe that cells in both PTC and HT are in a state of chronic inflammatory activation and do not respond to p53 and FAS-induced apoptosis signals. Chronic inflammation may promote apoptosis non-response. The molecular expression differences between PTC and HT mainly focus on the expression differences in the extracellular matrix, which activate/inhibit T cell immune responses, leading to different disease phenotypes. Papillary thyroid carcinoma Hashimoto's thyroiditis Expression profile comparative analysis Full Text Additional Declarations No competing interests reported. Supplementary Files 1.FinalResultintersectFC1Padj005allGroup1.xls 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. 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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-6689784","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":459259231,"identity":"7bbf8942-3853-4e14-8963-894b65d32653","order_by":0,"name":"Xuelu Xu","email":"","orcid":"","institution":"changxing County People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xuelu","middleName":"","lastName":"Xu","suffix":""},{"id":459259232,"identity":"a35ce01e-8c78-4da3-85ed-ef9f30595024","order_by":1,"name":"Yuqing Ma","email":"","orcid":"","institution":"changxing County People's 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analysis","lastPublishedDoi":"10.21203/rs.3.rs-6689784/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6689784/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003ePapillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT) are diseases where one is a \"cancer\" that has escaped immune system surveillance, and the other is an \"autoimmune disease\" that attacks the body's own systems. They appear to be antagonistic in form, but in reality, they can occur simultaneously. The similarities or differences in their gene molecular expression are worth in-depth discussion.\u003c/p\u003e\u003ch2\u003eResearch Methods\u003c/h2\u003e \u003cp\u003eThis study searched the GEO database, integrating 4 GEO datasets to compare the gene expression similarities and differences in thyroid tissues of papillary thyroid carcinoma (PTC), Hashimoto's thyroiditis (HT), and concurrent PTC and HT (PTC_HT) against normal tissue (Control). The limma software package was used to select differentially expressed genes compared to normal tissue (Control), followed by KEGG clustering and gene pathway interaction analysis. Finally, we verified the differentially expressed genes discovered in our collected PTC, HT, and adjacent cancer tissues.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eWe integrated and analyzed gene expression data from 166 tissue samples in the database, finding 202 genes with significant expression differences in PTC, HT, and PTC_HT pathological phenotypes. Moreover, these 202 genes showed consistent expression trends (i.e., same direction of increase or decrease) in the cells of the three pathological phenotypes. They are mainly inflammatory and chemokine factors (CXCL8, CXCL9, CXCL10, and IL8), with thyroid cells in all three diseases existing in an environment where chemokines activate inflammation. They also do not respond to p53 and FAS-induced apoptosis signals. Comparing genes with completely opposite expression trends between PTC and HT, we found these genes mainly concentrated in the ECM-receptor interaction pathway, involving genes such as FN1, LAMB1, and LAMC1. By combining DEGs and hubGenes, we found that differences in the FN1-DUSP6-ETV5-NFATC1/3 signaling axis may be the cause of different phenotypes in HT and PTC. QPCR and WB verification of collected PTC, HT, and adjacent cancer patient tissues also supported these findings.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eBased on the above results, we believe that cells in both PTC and HT are in a state of chronic inflammatory activation and do not respond to p53 and FAS-induced apoptosis signals. Chronic inflammation may promote apoptosis non-response. The molecular expression differences between PTC and HT mainly focus on the expression differences in the extracellular matrix, which activate/inhibit T cell immune responses, leading to different disease phenotypes.\u003c/p\u003e","manuscriptTitle":"Comparative Transcriptomic Analysis of Pathogenic Mechanisms in Papillary Thyroid Carcinoma and Hashimoto's Thyroiditis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-21 13:28:29","doi":"10.21203/rs.3.rs-6689784/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":"10a3b7db-443c-44c0-a9d1-94e006fabc07","owner":[],"postedDate":"May 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-23T03:08:31+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-21 13:28:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6689784","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6689784","identity":"rs-6689784","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}