{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T11:05:15Z","timestamp":1759057515372,"version":"3.40.5"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,5,27]],"date-time":"2019-05-27T00:00:00Z","timestamp":1558915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:sec><jats:title>Objectives\/Hypothesis<\/jats:title><jats:p>To establish comprehensive transcriptomic profiles of cholesteatoma perimatrix tissue and granulation tissue from chronic otitis media (COM) that did not develop cholesteatoma, which can indicate molecular pathways involved in the cholesteatoma perimatrix pathology and invasiveness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Retrospective Case Series.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Transcriptome data were obtained from cholesteatoma perimatrix tissue and COM granulation tissue by an Illumina iScan microarray. Differentially expressed genes (DEGs) were subsequently analyzed using both bioinformatical functional annotation and network analysis. Expression of candidate genes (<jats:italic>MMP9<\/jats:italic> and <jats:italic>LCN2<\/jats:italic>) was validated by quantitative reverse transcription\u2010polymerase chain reaction (qRT\u2010PCR) on a larger group of samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Analysis of the transcriptome led to the identification of 169 differentially expressed genes between investigated tissues. Bioinformatic analysis suggested that most significant biological processes involving DEGs were previously described in cholesteatoma pathology. Network analysis identified ERBB2, TFAP2A, and TP63 as major hubs of the DEGs molecular network. Furthermore, it was observed that the cellular component most significantly enriched in DEGs was extracellular space containing 47 DEGs. Using qRT\u2010PCR, it was confirmed that mRNA levels of the major extracellular hub (MMP9) are increased, whereas its interacting molecule (LCN2) mRNA levels were decreased in cholesteatoma perimatrix tissue compared to COM granulation tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The current study approach offers an overall look at molecular mechanisms that describe the cholesteatoma entity by focusing exclusively on the perimatrix processes in comparison to COM granulation tissue. The observed differences in gene expression between cholesteatoma perimatrix and COM granulation tissue could suggest novel markers potentially influenced by the perimatrix\u2013matrix molecular interplay, which is not present in COM without cholesteatoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA<\/jats:p><jats:p><jats:italic>Laryngoscope<\/jats:italic>, 130:E220\u2013E227, 2020<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.28084","type":"journal-article","created":{"date-parts":[[2019,5,27]],"date-time":"2019-05-27T14:59:15Z","timestamp":1558969155000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Perimatrix of middle ear cholesteatoma: A granulation tissue with a specific transcriptomic signature"],"prefix":"10.1002","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7932-9463","authenticated-orcid":false,"given":"Ivan","family":"Jovanovic","sequence":"first","affiliation":[{"name":"VIN\u010cA Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics University of Belgrade  Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"Zivkovic","sequence":"additional","affiliation":[{"name":"VIN\u010cA Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics University of Belgrade  Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Djuric","sequence":"additional","affiliation":[{"name":"VIN\u010cA Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics University of Belgrade  Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ljiljana","family":"Stojkovic","sequence":"additional","affiliation":[{"name":"VIN\u010cA Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics University of Belgrade  Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Snezana","family":"Jesic","sequence":"additional","affiliation":[{"name":"Medical Faculty University of Belgrade  Belgrade Serbia"},{"name":"Clinic for Otorhinolaryngology and Maxillofacial Surgery Clinical Centre of Serbia  Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Stankovic","sequence":"additional","affiliation":[{"name":"VIN\u010cA Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics University of Belgrade  Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,5,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-003-0623-x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.24890"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1808-86942011000300012"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1997.tb51882.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/854024"},{"issue":"9","key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1288\/00005537-198609000-00002","article-title":"Cholesteatoma staging","volume":"96","author":"Meyerhoff WL","year":"1986","journal-title":"Laryngoscope"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.20841"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/coa.12900"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-11028"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200303000-00009"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anl.2015.04.010"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0003489414527229"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.09.042"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2004-5-10-r80"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btn224"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btn647"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/19.2.185"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1239"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku443"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.052"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1147"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/00034894941030S507"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/MLG.0b013e31814faafa"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-1811(00)00141-9"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00603.x"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-0232"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/408169"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mlg.0000147934.21638.d8"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.3109\/00016489.2013.847282"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(00)00454-6"},{"key":"e_1_2_6_35_1","first-page":"1701","article-title":"A family of AP\u20102 proteins regulates c\u2010erbB\u20102 expression in mammary carcinoma","volume":"13","author":"Bosher JM","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80275-0"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2010.119"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/00016480802251591"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2006-7-5-216"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/00016480500475633"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052718"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.24176"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijmbs.ijmbs_33_18"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2007.07.003"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1418"},{"key":"e_1_2_6_46_1","first-page":"621","article-title":"Stromal expression of matrix metalloprotease\u20109 in middle ear cholesteatomas","volume":"21","author":"Shibosawa E","year":"2000","journal-title":"Am J Otol"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/35036374"},{"key":"e_1_2_6_48_1","first-page":"793","article-title":"Angiogenesis and angiogenic growth factors in middle ear cholesteatoma","volume":"21","author":"Sudhoff H","year":"2000","journal-title":"Am J Otol"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.07.021"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)82217-7"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106089200"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers6020796"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200305000-00008"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348947208100102"}],"container-title":["The Laryngoscope"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lary.28084","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/lary.28084","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lary.28084","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T02:23:36Z","timestamp":1694053416000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/lary.28084"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,27]]},"references-count":53,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["10.1002\/lary.28084"],"URL":"https:\/\/doi.org\/10.1002\/lary.28084","archive":["Portico"],"relation":{},"ISSN":["0023-852X","1531-4995"],"issn-type":[{"type":"print","value":"0023-852X"},{"type":"electronic","value":"1531-4995"}],"subject":[],"published":{"date-parts":[[2019,5,27]]},"assertion":[{"value":"2019-03-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}