{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:54:12Z","timestamp":1789480452369,"version":"build-2803163510"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870711"],"award-info":[{"award-number":["81870711"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Objective<\/jats:title><jats:p>To screen for obstructive sleep apnea (OSA) biomarkers, isobaric tags for relative and absolute quantitation (iTRAQ)-labeled quantitative proteomics assay was used to identify differentially expressed proteins (DEPs) during chronic intermittent hypoxia (CIH).<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Method<\/jats:title><jats:p>The iTRAQ technique was applied to compare DEPs in the serum of a CIH rat model and control group. Biological analysis of DEPs was performed using Gene Ontology and Kyoto Encyclopedia to explore related biological functions and signaling pathways. Enzyme-linked immunosorbent assay (ELISA) was performed to validate their expression in sera from patients with OSA and CIH rats.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>Twenty-three DEPs (fold change \u22651.2 or \u22640.833,<jats:italic>p<\/jats:italic>&lt;0.05) were identified, and two DEPs (unique peptides&gt;3 and higher coverage) were further verified by ELISA in the CIH rat model and OSA subject: apolipoprotein A-IV (APOA4,<jats:italic>p<\/jats:italic>&lt;0.05) and Tubulin alpha-1A chain (TUBA1A,<jats:italic>p<\/jats:italic>&lt;0.05). Both groups showed significant differences in the expression levels of DEPs between the CIH and control groups and the severe OSA and non-OSA groups. APOA4 was found to be upregulated and TUBA1A downregulated in both the sera from OSA patients and CIH rats, on comparing proteomics results with clinical results. There were two pathways that involved three DEPs, the mitogen-activated protein kinase (MAPK) signaling pathway (<jats:italic>p<\/jats:italic>&lt;0.05) and cytokine-cytokine receptor interaction (<jats:italic>p<\/jats:italic>&lt;0.05).<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusion<\/jats:title><jats:p>APOA4 and TUBA1A may be potential novel biomarkers for CIH and OSA, and may play an important role in the development of OSA complications.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0253943","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T17:40:24Z","timestamp":1624988424000},"page":"e0253943","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Novel proteins associated with chronic intermittent hypoxia and obstructive sleep apnea: From rat model to clinical evidence"],"prefix":"10.1371","volume":"16","author":[{"given":"Xiaojun","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5874-6049","authenticated-orcid":true,"given":"Shisheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinming","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinglai","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiying","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiying","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"issue":"9","key":"pone.0253943.ref001","first-page":"1155","article-title":"Obstructive sleep apnea: diagnosis, epidemiology, and economics","volume":"55","author":"VK Kapur","year":"2010","journal-title":"Respiratory Care"},{"issue":"7\u20138","key":"pone.0253943.ref002","article-title":"Current challenges in the diagnosis and treatment of obstructive sleep apnea syndrome in the elderly","volume":"130","author":"G Ia Nn Ella","year":"2020","journal-title":"Polskie Archiwum Medycyny Wewn\u0229trznej"},{"issue":"3","key":"pone.0253943.ref003","doi-asserted-by":"crossref","DOI":"10.1007\/s00405-020-06316-w","article-title":"Olfactory function in patients with obstructive sleep apnea: a meta-analysis study","volume":"278","author":"G Iannella","year":"2021","journal-title":"European Archives of Oto-Rhino-Laryngology"},{"key":"pone.0253943.ref004","first-page":"233","article-title":"Obstructive sleep apnea syndrome: natural history, diagnosis, and emerging treatment options","volume":"2","author":"T Gharibeh","year":"2010","journal-title":"Nature & Science of Sleep"},{"issue":"4","key":"pone.0253943.ref005","doi-asserted-by":"crossref","DOI":"10.1007\/s11325-019-01985-2","article-title":"Outcome predictors for non-resective pharyngoplasty alone or as a part of multilevel surgery, in obstructive sleep apnea-hypopnea syndrome","volume":"24","author":"F Missale","year":"2020","journal-title":"Sleep and Breathing"},{"issue":"4","key":"pone.0253943.ref006","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.tcm.2015.10.004","article-title":"Metabolic syndrome update.","volume":"26","author":"SM Grundy","year":"2016","journal-title":"Trends in cardiovascular medicine"},{"issue":"4","key":"pone.0253943.ref007","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/j.1479-8425.2012.00536.x","article-title":"Plasma proteomic analysis in patients with obstructive sleep apnea syndrome","volume":"10","author":"TS Masao Shinohara","year":"2012","journal-title":"Sleep & Biological Rhythms"},{"key":"pone.0253943.ref008","doi-asserted-by":"crossref","unstructured":"Liu YY, Gao L, Jing Z, Huang YB, editors. 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