{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T13:34:02Z","timestamp":1778420042971,"version":"3.51.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T00:00:00Z","timestamp":1664236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Although many pathological mechanisms and etiological hypotheses of acute unilateral vestibulopathy (AUVP) have been reported, but the actual etiology remains to be elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study was based on comprehensive bioinformatics to identify the critical genes of AUVP and explore its pathological mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gene expression profiles of AUVP and normal samples were collected from GSE146230 datasets of the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was constructed, and the WGCNA R-package extracted significant modules. The limma R-package was applied to identify differentially expressed genes (DEGs). The common genes of practical modules and DEGs were screened for GO and KEGG pathways analysis. The protein\u2013protein interaction (PPI) layout and hub genes validation was created by Cytoscape software using the link from the STRING database. The functions of hub genes were predicted through the CTD (comparative genetics database).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 332 common genes were screened from practical modules and DEGs. Functional enrichment analysis revealed that these genes were predominantly associated with inflammation and infection. After construction of PPI, expressions of hub genes, and drawing ROC curves, LILRB2, FPR1, AQP9, and LILRA1 are highly expressed in AUVP (<jats:italic>p<\/jats:italic> &amp;lt; 0.05) and have a certain diagnostic efficacy for AUVP (AUC &amp;gt; 0.7), so they were selected as hub genes. The functions of hub genes suggested that the occurrence of AUVP may be related to inflammation, necrosis, hepatomegaly, and other conditions in CTD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>LILRB2, FPR1, AQP9, and LILRA1 may play essential roles in developing AUVP, providing new ideas for diagnosing and treating AUVP.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.987076","type":"journal-article","created":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T15:10:26Z","timestamp":1664291426000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of hub genes and pathophysiological mechanism related to acute unilateral vestibulopathy by integrated bioinformatics analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Yajing","family":"Cheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianrong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bihua","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3233\/VES-220201","article-title":"Acute unilateral vestibulopathy\/vestibular neuritis: diagnostic criteria","author":"Strupp","year":"2021","journal-title":"J Vestib Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"81","DOI":"10.12701\/yujm.2021.01228","article-title":"Current diagnosis and treatment of vestibular neuritis: a narrative review","volume":"39","author":"Bae","year":"2022","journal-title":"J Yeungnam Med Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/B978-0-444-63437-5.00005-4","article-title":"The epidemiology of dizziness and vertigo","volume":"137","author":"Neuhauser","year":"2016","journal-title":"Handb Clin Neurol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s10072-014-1912-4","article-title":"Incidence, seasonality and comorbidity in vestibular neuritis","volume":"36","author":"Adamec","year":"2015","journal-title":"Neurol Sci."},{"key":"B5","first-page":"323","article-title":"Vestibular neuronitis. Vestibular paralysis with special characteristics","volume":"27","author":"Depondt","year":"1973","journal-title":"Acta Otorhinolaryngol Belg"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1212\/01.wnl.0000244473.84246.76","article-title":"Low recurrence rate of vestibular neuritis: a long-term follow-up","volume":"67","author":"Huppert","year":"2006","journal-title":"Neurology."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.3109\/00016489.2011.593551","article-title":"Recurrence of vertigo in patients with vestibular neuritis","volume":"131","author":"Kim","year":"2011","journal-title":"Acta Otolaryngol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1055\/s-0038-1666815","article-title":"Epidemiology of vestibular impairments in a pediatric population","volume":"39","author":"Wiener-Vacher","year":"2018","journal-title":"Semin Hear."},{"key":"B9","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1159\/000490275","article-title":"Vestibular neuritis: recent advances in etiology, diagnostic evaluation, and treatment","volume":"82","author":"Le","year":"2019","journal-title":"Adv Otorhinolaryngol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1056\/NEJMcp021154","article-title":"Clinical practice. Vestibular neuritis","volume":"348","author":"Baloh","year":"2003","journal-title":"N Engl J Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1177\/000348940211100201","article-title":"The three faces of vestibular ganglionitis","volume":"111","author":"Gacek","year":"2002","journal-title":"Ann Otol Rhinol Laryngol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/S0194-5998(96)70251-6","article-title":"Vestibular neuritis: clinical-pathologic correlation","volume":"114","author":"Baloh","year":"1996","journal-title":"Otolaryngol Head Neck Surg."},{"key":"B13","volume-title":"Pathology of the Ear","author":"Schuknecht","year":"1993"},{"key":"B14","doi-asserted-by":"publisher","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: archive for functional genomics data sets\u2013update","volume":"41","author":"Barrett","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1111\/cei.13083","article-title":"RNA-sequencing study of peripheral blood mononuclear cells in sporadic Meniere's disease patients: possible contribution of immunologic dysfunction to the development of this disorder","volume":"192","author":"Sun","year":"2018","journal-title":"Clin Exp Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.3389\/fimmu.2019.01229","article-title":"Differential proinflammatory signature in vestibular migraine and meniere disease","volume":"10","author":"Flook","year":"2019","journal-title":"Front Immunol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"938740","DOI":"10.3389\/fneur.2022.938740","article-title":"Transcriptional down-regulation of major histocompatibility complex as a possible pathogenesis for Meniere's disease","volume":"13","author":"Choi","year":"2022","journal-title":"Front Neurol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"363","DOI":"10.3233\/VES-200044","article-title":"Neutrophil-mediated immune response as a possible mechanism of acute unilateral vestibulopathy","volume":"30","author":"Oh","year":"2020","journal-title":"J Vestib Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinformatics."},{"key":"B20","doi-asserted-by":"publisher","first-page":"8551","DOI":"10.1002\/jcp.26440","article-title":"The key genes underlying pathophysiology association between the type 2-diabetic and colorectal cancer","volume":"233","author":"Peng","year":"2018","journal-title":"J Cell Physiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.3390\/jcm8081160","article-title":"Identification of prognostic candidate genes in breast cancer by integrated bioinformatic analysis","volume":"8","author":"Wang","year":"2019","journal-title":"J Clin Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"8594658","DOI":"10.1155\/2022\/8594658","article-title":"A nove hypoxia-related gene signature with strong predicting ability in non-small-cell lung cancer identified by comprehensive profiling","volume":"2022","author":"Yang","year":"2022","journal-title":"Int J Genomics."},{"key":"B23","doi-asserted-by":"publisher","first-page":"15333175211046123","DOI":"10.1177\/15333175211046123","article-title":"Identification of hub genes related to Alzheimer's disease and major depressive disorder","volume":"36","author":"Cheng","year":"2021","journal-title":"Am J Alzheimers Dis Other Demen."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma power differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimenta datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1893351","DOI":"10.1155\/2022\/1893351","article-title":"Identification of hub genes for early diagnosis and predicting prognosis in colon adenocarcinoma","volume":"2022","author":"Xu","year":"2022","journal-title":"Biomed Res Int."},{"key":"B27","doi-asserted-by":"publisher","first-page":"109326","DOI":"10.1016\/j.abb.2022.109326","article-title":"The protective effects of curcumin on metabolic syndrome and its components: in-silico analysis for genes, transcription factors, and microRNAs involved","volume":"727","author":"Nguyen","year":"2022","journal-title":"Arc Biochem Biophys."},{"key":"B28","doi-asserted-by":"publisher","first-page":"4189","DOI":"10.1200\/JCO.2007.11.5964","article-title":"Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity","volume":"26","author":"Hegi","year":"2008","journal-title":"J Clin Oncol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"459048","DOI":"10.1155\/2014\/459048","article-title":"Is vestibular neuritis an immune related vestibular neuropathy inducing vertigo?","volume":"2014","author":"Greco","year":"2014","journal-title":"J Immunol Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1055\/s-0033-1354598","article-title":"Vestibular neuritis","volume":"33","author":"Jeong","year":"2013","journal-title":"Semin Neurol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2990","DOI":"10.4049\/jimmunol.1003078","article-title":"HLA class I allelic sequence and conformation regulate leukocyte Ig-like receptor binding","volume":"186","author":"Jones","year":"2011","journal-title":"J Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1073\/pnas.0337567100","article-title":"Activation of human eosinophils through leukocyte immunoglobulin-like receptor 7","volume":"100","author":"Tedla","year":"2003","journal-title":"Proc Natl Acad Sci USA."},{"key":"B33","doi-asserted-by":"publisher","first-page":"857","DOI":"10.3389\/fimmu.2020.00857","article-title":"Leukocyte immunoglobulin-like receptors (LILRs) on human neutrophils: modulators of infection and immunity","volume":"11","author":"Lewis Marffy","year":"2020","journal-title":"Front Immunol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"19536","DOI":"10.1074\/jbc.M603076200","article-title":"Crystal structure of thehuman monocyte-activating receptor, \u201cGroup 2\u201d leukocyte Ig-like receptor A5 (LILRA5\/LIR9\/ILT11)","volume":"281","author":"Shiroishi","year":"2006","journal-title":"J Biol Chem."},{"key":"B35","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1038\/ni961","article-title":"Crystal structure of HLA-A2 bound to LIR-1, a host and viral major histocompatibility complex receptor","volume":"4","author":"Willcox","year":"2003","journal-title":"Nat Immunol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"3552","DOI":"10.1002\/1521-4141(200012)30:12<3552::AID-IMMU3552>3.0.CO;2-L","article-title":"Functional characterization of HLA-F and binding of HLA-F tetramers to ILT2 and ILT4 receptors","volume":"30","author":"Lepin","year":"2000","journal-title":"Eur J Immunol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1002\/(SICI)1521-4141(199901)29:01<277::AID-IMMU277>3.0.CO;2-4","article-title":"The ILT2(LIR1) and CD94\/NKG2A NK cell receptors respectively recognize HLA-G1 and HLA-E molecules co- expressed on target cells","volume":"29","author":"Navarro","year":"1999","journal-title":"Eur J Immunol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"17957","DOI":"10.1073\/pnas.1221535110","article-title":"Exocytosis acts as a modulator of the ILT4-mediated inhibition of neutrophil functions","volume":"110","author":"Baudhuin","year":"2013","journal-title":"Proc Natl Acad Sci USA."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.1007\/s11064-010-0301-5","article-title":"Expression and signaling of formyl-peptide receptors in the brain","volume":"35","author":"Cattaneo","year":"2010","journal-title":"Neurochem Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.3390\/nu13051418","article-title":"Formyl peptide receptor (FPR)1 modulation by resveratrol in an LPS- induced neuroinflammatory animal model","volume":"13","author":"Calvello","year":"2021","journal-title":"Nutrients."},{"key":"B41","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1007\/s12031-017-0924-y","article-title":"Formyl peptide receptor 1-mediated glial cell activation in a mouse model of cuprizone-induced demyelination","volume":"62","author":"Bihler","year":"2017","journal-title":"J Mol Neurosci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s13578-018-0211-9","article-title":"Function of aquaporins in sepsis: a systematic review","volume":"8","author":"Rump","year":"2018","journal-title":"Cell Biosci"},{"key":"B43","doi-asserted-by":"publisher","first-page":"15319","DOI":"10.1038\/srep15319","article-title":"Aquaporin-9-expressing neutrophils are required for the establishment of contact hypersensitivity","volume":"5","author":"Moniaga","year":"2015","journal-title":"Sci Rep."},{"key":"B44","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1097\/SHK.0000000000000218","article-title":"Enhanced expression of aquaporin 9 in activated polymorphonuclear leukocytes in patients with systemic inflammatory response syndrome","volume":"42","author":"Matsushima","year":"2014","journal-title":"Shock."},{"key":"B45","doi-asserted-by":"publisher","first-page":"530","DOI":"10.3390\/biom12040530","article-title":"Cellular distribution of brain aquaporins and their contribution to cerebrospinal fluid homeostasis and hydrocephalus","volume":"12","author":"Trillo-Contreras","year":"2022","journal-title":"Biomolecules."},{"key":"B46","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.neuroscience.2004.05.042","article-title":"Distribution of aquaporin 9 in the adult rat brain: preferential expression in catecholaminergic neurons and in glial cells","volume":"128","author":"Badaut","year":"2004","journal-title":"Neuroscience."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.987076\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T15:10:32Z","timestamp":1664291432000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.987076\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,27]]},"references-count":46,"alternative-id":["10.3389\/fneur.2022.987076"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2022.987076","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,27]]},"article-number":"987076"}}