{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:40:23Z","timestamp":1777873223224,"version":"3.51.4"},"reference-count":47,"publisher":"Frontiers Media SA","issue":"1","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801616"],"award-info":[{"award-number":["81801616"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100381"],"award-info":[{"award-number":["82100381"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Exp Biol Med (Maywood)"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>The calcific aortic valve disease (CAVD) develops as an aortic valve sclerosis and progresses to an advanced form of stenosis. In many biological fields, bioinformatics becomes a fundamental component. The key mechanisms involved in CAVD are discovered with the use of bioinformatics to investigate gene function and pathways. We downloaded the original data (GSE51472) from the Gene Expression Omnibus (GEO) database ( http:\/\/www.ncbi.nlm.nih.gov\/geo\/ ). After standardization, 2978 differentially expressed genes (DEGs) were identified from the data sets GSE51472 containing samples from normal, calcified, and sclerotic aortic valves. Analysis of DEGs based on the series test of clusters (STCs) revealed the two most significant patterns. Based on the result of the STC, the functional enrichment analysis of gene ontology (GO) was conducted to investigate the molecular function (MF), biological process (BP), and cell compound (CC) of the DEGs. With a p value of 0.01, DEGs associated with \u201cchronic inflammation,\u201d \u201cT-cell receptor complexes,\u201d and \u201cantigen binding\u201d had the highest significance within BP, CC, and MF. DEG enrichment in signaling pathways was analyzed using KEGG pathway enrichment. Using a p\u2009&lt;\u20090.05 level of significance, the most enriched biological pathways related to CAVD were \u201cChemokine signaling pathway,\u201d \u201cCytokine-cytokine receptor interaction,\u201d \u201cTuberculosis,\u201d \u201cPI3K-Akt signaling pathway,\u201d and \u201cTranscriptional misregulation in cancer.\u201d Finally, the construction of gene co-expression networks and pathway networks illustrated the pathogensis of CAVD. TLR2, CD86, and TYROBP were identified as hub genes for the development of CAVD. Moreover, \u201cMAPK signaling pathway,\u201d \u201cApoptosis,\u201d and \u201cPathways in cancer\u201d were regarded as the core pathways among the samples of normal, sclerotic and calcified aortic valve samples.<\/jats:p>","DOI":"10.1177\/15353702221118088","type":"journal-article","created":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T02:14:33Z","timestamp":1663985673000},"page":"52-60","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of key genes involved in calcific aortic valve disease based on integrated bioinformatics analysis"],"prefix":"10.3389","volume":"248","author":[{"given":"Ye-Hong","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Cardiology, Shanghai East Hospital, Shanghai Tongji University School of Medicine, Shanghai 200120, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit, Shanghai East Hospital, Shanghai Tongji University School of Medicine, Shanghai 200120, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan-Feng","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Shanghai East Hospital, Shanghai Tongji University School of Medicine, Shanghai 200120, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai East Hospital, Shanghai Tongji University School of Medicine, Shanghai 200120, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8680-9112","authenticated-orcid":false,"given":"Meng-Lei","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shanghai East Hospital, Shanghai Tongji University School of Medicine, Shanghai 200120, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"bibr1-15353702221118088","volume":"16","author":"Bach DS","year":"2007","journal-title":"J Heart Valve Dis"},{"key":"bibr2-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.486738"},{"key":"bibr3-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(93)90249-Z"},{"key":"bibr4-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(96)00563-3"},{"key":"bibr5-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2011.164"},{"key":"bibr6-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afh175"},{"key":"bibr7-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1590\/S0066-782X2009000900015"},{"key":"bibr8-15353702221118088","volume":"16","author":"O\u2019Brien KD","year":"1996","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"bibr9-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.19.5.1218"},{"key":"bibr10-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1136\/heart.85.6.601"},{"key":"bibr11-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2014.03.029"},{"key":"bibr12-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.006767"},{"key":"bibr13-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1093\/bfgp\/elu044"},{"key":"bibr14-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apcsb.2014.06.008"},{"key":"bibr15-15353702221118088","doi-asserted-by":"publisher","DOI":"10.3109\/07853890.2015.1059955"},{"key":"bibr16-15353702221118088","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.49332"},{"key":"bibr17-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00100.2019"},{"key":"bibr18-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80119-3"},{"key":"bibr19-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-07-0067"},{"key":"bibr20-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2006.12.002"},{"key":"bibr21-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1080\/08977190412331279890"},{"key":"bibr22-15353702221118088","volume":"17","author":"Jensen ED","year":"2007","journal-title":"Crit Rev Eukaryot Gene Expr"},{"key":"bibr23-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.001115"},{"key":"bibr24-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00137.2007"},{"key":"bibr25-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.654913"},{"key":"bibr26-15353702221118088","volume":"13","author":"Kaden JJ","year":"2004","journal-title":"J Heart Valve Dis"},{"key":"bibr27-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000220441.42041.20"},{"key":"bibr28-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23755"},{"key":"bibr29-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.014266"},{"key":"bibr30-15353702221118088","volume":"165","author":"McAdam AJ","year":"1998","journal-title":"Immunol Rev"},{"key":"bibr31-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.14.1.233"},{"key":"bibr32-15353702221118088","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.155.11.5124"},{"key":"bibr33-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119465"},{"key":"bibr34-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1038\/28204"},{"key":"bibr35-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(97)00135-4"},{"key":"bibr36-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1097\/MCA.0b013e3282eff1ad"},{"key":"bibr37-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2017.02.012"},{"key":"bibr38-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050986"},{"key":"bibr39-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00720.x"},{"key":"bibr40-15353702221118088","first-page":"4995","volume":"22","author":"Wang HM","year":"2018","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"bibr41-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00031-10"},{"key":"bibr42-15353702221118088","doi-asserted-by":"publisher","DOI":"10.3109\/09553002.2014.996261"},{"key":"bibr43-15353702221118088","doi-asserted-by":"crossref","first-page":"58","DOI":"10.14348\/molcells.2015.2231","volume":"38","author":"Nguyen CT","year":"2015","journal-title":"Mol Cells"},{"key":"bibr44-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2015.02.015"},{"key":"bibr45-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2015.09.077"},{"key":"bibr46-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1159\/000369126"},{"key":"bibr47-15353702221118088","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-014-0743-3"}],"container-title":["Experimental Biology and Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15353702221118088","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/15353702221118088","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15353702221118088","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:51:58Z","timestamp":1777571518000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ebm-journal.org\/journals\/experimental-biology-and-medicine\/articles\/10.1177\/15353702221118088\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,23]]},"references-count":47,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1177\/15353702221118088"],"URL":"https:\/\/doi.org\/10.1177\/15353702221118088","relation":{},"ISSN":["1535-3702","1535-3699"],"issn-type":[{"value":"1535-3702","type":"print"},{"value":"1535-3699","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,23]]}}}