{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:25:25Z","timestamp":1785817525720,"version":"3.56.0"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20232BAB216010 and 20242BAB25433"],"award-info":[{"award-number":["20232BAB216010 and 20242BAB25433"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009102","name":"Education Department of Jiangxi Province","doi-asserted-by":"publisher","award":["GJJ210251"],"award-info":[{"award-number":["GJJ210251"]}],"id":[{"id":"10.13039\/501100009102","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural incubation Program of the second affiliated Hospital of Nanchang University","award":["2022YNFY12013"],"award-info":[{"award-number":["2022YNFY12013"]}]},{"name":"Jiangxi province health science and technology plan project","award":["(202510325"],"award-info":[{"award-number":["(202510325"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec023\">\n<jats:title>Background<\/jats:title>\n<jats:p>Thyroid eye disease (TED) is one of the most common autoimmune orbital diseases in adults. The early diagnosis and effective treatment of TED is a worldwide problem. Extracellular proteins may act as indicators in bodily fluids. Our research sought to identify the roles of extracellular proteins and possible biomarkers in TED using a bioinformatics study.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec024\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Data from Gene Expression Omnibus (GEO) were acquired to create the TED expression profiles. The annotation database screened extracellular proteins with differentially expressed genes (EP-DEGs). To investigate both the function and the route of EP-DEGs, GO and KEGG were utilized. Hub genes and protein-protein interaction (PPI) networks among EP-DEGs were discovered. Key EP-DEGs\u2019 diagnostic potency was assessed using the receiver operating characteristic (ROC) curve.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec025\">\n<jats:title>Results<\/jats:title>\n<jats:p>102 EP-DEGs underwent screening. The extracellular matrix, which contains collagen, the receptor-ligand activity, the interaction between cytokines and their receptors, and the complement and coagulation cascades route, were all enhanced in EP-DEGs. The EP-DEG PPI network contained 233 edges and 78 nodes. We discovered 21 extracellular proteins that interacted with EGFR in addition to 3 major extracellular proteins, EGFR, CD44, and CXCL8, all of which had significant values of AUC (&gt; 0.7).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec026\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>In conclusion, EGFR, CD44, and CXCL8 may be the potential biomarker in the TED. this research gives us a theoretical foundation for understanding how TED pathogenesis occurs.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0322415","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T17:58:07Z","timestamp":1745949487000},"page":"e0322415","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Identification of key extracellular proteins as the potential biomarkers in thyroid eye disease"],"prefix":"10.1371","volume":"20","author":[{"given":"Shasha","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangbao","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1660-563X","authenticated-orcid":true,"given":"Zhiwei","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"pone.0322415.ref001","doi-asserted-by":"crossref","first-page":"952954","DOI":"10.3389\/fimmu.2022.952954","article-title":"Research progress on the pathogenesis of Graves\u2019 ophthalmopathy: Based on immunity, noncoding RNA and exosomes","volume":"13","author":"J Zheng","year":"2022","journal-title":"Front Immunol"},{"key":"pone.0322415.ref002","doi-asserted-by":"crossref","first-page":"615993","DOI":"10.3389\/fendo.2020.615993","article-title":"Epidemiology, Natural History, Risk Factors, and Prevention of Graves\u2019 Orbitopathy","volume":"11","author":"L Bartalena","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"pone.0322415.ref003","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s40246-022-00412-0","article-title":"Construction of the coexpression network involved in the pathogenesis of thyroid eye disease via bioinformatics analysis","volume":"16","author":"J Hu","year":"2022","journal-title":"Hum Genomics"},{"issue":"7","key":"pone.0322415.ref004","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.4103\/ijo.IJO_3217_21","article-title":"Update on thyroid eye disease: Regional variations in prevalence, diagnosis, and management","volume":"70","author":"CY 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