PMID- 32619300 OWN - NLM STAT- MEDLINE DCOM- 20210128 LR - 20220202 IS - 1531-4995 (Electronic) IS - 0023-852X (Print) IS - 0023-852X (Linking) VI - 131 IP - 2 DP - 2021 Feb TI - Proteomic and Genomic Methylation Signatures of Idiopathic Subglottic Stenosis. PG - E540-E546 LID - 10.1002/lary.28851 [doi] AB - OBJECTIVE: Idiopathic subglottic stenosis (iSGS) is a chronic inflammatory condition that causes dyspnea and affects middle-aged women of White race and non-Latino 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. STUDY DESIGN: Molecular analysis of clinical biospecimens. METHODS: We collected subglottic tissue biopsies from 12 patients during direct laryngoscopy, immediately prior to surgical treatment of iSGS; as well as from 4 age-, sex-, and race/ethnicity-matched control patients undergoing other direct laryngoscopic procedures. We isolated protein and genomic DNA, acquired proteomic data using label-free quantitative mass spectrometry techniques, and acquired genome-wide 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. RESULTS: 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-based 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 (BTD). Follow-up analysis showed elevated plasma BTD activity in iSGS patients compared to both controls and published normative data. CONCLUSION: 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. LEVEL OF EVIDENCE: Not applicable Laryngoscope, 131:E540-E546, 2021. CI - (c) 2020 The American Laryngological, Rhinological and Otological Society, Inc. FAU - Schoeff, Stephen S AU - Schoeff SS AD - Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, U.S.A. FAU - Shi, Xudong AU - Shi X AD - Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, U.S.A. FAU - Young, William G AU - Young WG AD - Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, U.S.A. FAU - Whited, Chad W AU - Whited CW AD - Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, U.S.A. FAU - Soni, Resha S AU - Soni RS AD - Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, U.S.A. FAU - Liu, Peng AU - Liu P AD - Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, U.S.A. FAU - Ong, Irene M AU - Ong IM AD - Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, U.S.A. AD - Department of Obstetrics and Gynecology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, U.S.A. FAU - Dailey, Seth H AU - Dailey SH AUID- ORCID: 0000-0002-3299-3014 AD - Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, U.S.A. FAU - Welham, Nathan V AU - Welham NV AUID- ORCID: 0000-0003-3484-3455 AD - Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, U.S.A. LA - eng GR - R01DC010777/DC/NIDCD NIH HHS/United States GR - R01 DC004428/DC/NIDCD NIH HHS/United States GR - P30 CA014520/CA/NCI NIH HHS/United States GR - R01DC004428/DC/NIDCD NIH HHS/United States GR - R01 DC010777/DC/NIDCD NIH HHS/United States GR - P30CA014520/CA/NCI NIH HHS/United States GR - P30CA014520/CA/NCI NIH HHS/United States GR - R01DC004428/DC/NIDCD NIH HHS/United States GR - R01DC010777/DC/NIDCD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200703 PL - United States TA - Laryngoscope JT - The Laryngoscope JID - 8607378 RN - 0 (Biomarkers) RN - 6SO6U10H04 (Biotin) SB - IM MH - Adult MH - Aged MH - Biomarkers MH - Biopsy MH - Biotin/metabolism MH - Case-Control Studies MH - *DNA Methylation MH - Female MH - Humans MH - Laryngostenosis/*etiology/genetics/metabolism/pathology MH - Larynx/metabolism/pathology MH - Middle Aged MH - *Proteomics/methods PMC - PMC7779687 MID - NIHMS1609379 OTO - NOTNLM OT - Biotin, biotinidase, dyspnea, fibrosis, inflammation, metabolism, 'omics, stenosis COIS- The authors have no other funding, financial relationships, or conflicts of interest to disclose. EDAT- 2020/07/04 06:00 MHDA- 2021/01/29 06:00 PMCR- 2022/02/01 CRDT- 2020/07/04 06:00 PHST- 2020/03/23 00:00 [received] PHST- 2020/05/13 00:00 [revised] PHST- 2020/05/15 00:00 [accepted] PHST- 2020/07/04 06:00 [pubmed] PHST- 2021/01/29 06:00 [medline] PHST- 2020/07/04 06:00 [entrez] PHST- 2022/02/01 00:00 [pmc-release] AID - 10.1002/lary.28851 [doi] PST - ppublish SO - Laryngoscope. 2021 Feb;131(2):E540-E546. doi: 10.1002/lary.28851. Epub 2020 Jul 3.