{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:13:00Z","timestamp":1785892380398,"version":"3.56.0"},"reference-count":63,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T00:00:00Z","timestamp":1593734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"The National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA014520"],"award-info":[{"award-number":["P30CA014520"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01DC004428"],"award-info":[{"award-number":["R01DC004428"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01DC010777"],"award-info":[{"award-number":["R01DC010777"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Idiopathic subglottic stenosis (iSGS) is a chronic inflammatory condition that causes dyspnea and affects middle\u2010aged women of White race and non\u2010Latino or Hispanic ethnicity. To better characterize its phenotype and pathogenesis, we assessed the proteomic and genomic methylation signatures of subglottic tissue collected from iSGS patients compared to controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Molecular analysis of clinical biospecimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected subglottic tissue biopsies from 12 patients during direct laryngoscopy, immediately prior to surgical treatment of iSGS; as well as from 4 age\u2010, sex\u2010, and race\/ethnicity\u2010matched control patients undergoing other direct laryngoscopic procedures. We isolated protein and genomic DNA, acquired proteomic data using label\u2010free quantitative mass spectrometry techniques, and acquired genome\u2010wide methylation data using bisulfite conversion and a microarray platform. We compared molecular profiles across the iSGS and control groups, and with respect to clinical course in the iSGS group. Eight of the 12 iSGS patients underwent subsequent blood collection and plasma isolation for further assessment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Proteomic analysis revealed 42 differentially abundant proteins in the iSGS biopsies compared to controls, inferring enrichment of biological pathways associated with early wound healing, innate immunity, matrix remodeling, and metabolism. Proteome\u2010based hierarchical clustering organized patients into two iSGS and one control subgroups. Methylation analysis revealed five hypermethylated genes in the iSGS biopsies compared to controls, including the biotin recycling enzyme biotinidase (<jats:italic>BTD<\/jats:italic>). Follow\u2010up analysis showed elevated plasma BTD activity in iSGS patients compared to both controls and published normative data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>iSGS exhibits distinct proteomic and genomic methylation signatures. These signatures expand current understanding of the iSGS phenotype, support the possibility of disease subgroups, and should inform the direction of future experimental studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>Not applicable <jats:italic>Laryngoscope<\/jats:italic>, 131:E540\u2013E546, 2021<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.28851","type":"journal-article","created":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T19:38:14Z","timestamp":1593805094000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Proteomic and Genomic Methylation Signatures of Idiopathic Subglottic Stenosis"],"prefix":"10.1002","volume":"131","author":[{"given":"Stephen S.","family":"Schoeff","sequence":"first","affiliation":[{"name":"Division of Otolaryngology \u2013 Head and Neck Surgery, Department of Surgery University of Wisconsin School of Medicine and Public Health  Madison 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U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Resha S.","family":"Soni","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology \u2013 Head and Neck Surgery, Department of Surgery University of Wisconsin School of Medicine and Public Health  Madison Wisconsin U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Informatics University of Wisconsin School of Medicine and Public Health  Madison Wisconsin U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene M.","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Informatics University of Wisconsin School of Medicine and Public Health  Madison Wisconsin U.S.A."},{"name":"Department of Obstetrics and Gynecology University of Wisconsin School of Medicine and Public Health  Madison Wisconsin 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