Identification of novel cholesteatoma-related gene expression signatures using full-genome microarrays
Cholesteatoma is a gradually expanding destructive epithelial lesion within the middle ear. It can cause extensive local tissue destruction in the temporal bone and can initially lead to the development of conductive hearing loss via ossicular erosion. As the disease progresses, sensorineural hearin...
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| creator | Klenke, Christin Janowski, Sebastian Borck, Daniela Widera, Darius Ebmeyer, Jörg Kalinowski, Jörn Leichtle, Anke Hofestädt, Ralf Upile, Tahwinder Kaltschmidt, Christian Kaltschmidt, Barbara Sudhoff, Holger |
| description | Cholesteatoma is a gradually expanding destructive epithelial lesion within the middle ear. It can cause extensive local tissue destruction in the temporal bone and can initially lead to the development of conductive hearing loss via ossicular erosion. As the disease progresses, sensorineural hearing loss, vertigo or facial palsy may occur. Cholesteatoma may promote the spread of infection through the tegmen of the middle ear and cause meningitis or intracranial infections with abscess formation. It must, therefore, be considered as a potentially life-threatening middle ear disease.
In this study, we investigated differentially expressed genes in human cholesteatomas in comparison to regular auditory canal skin using Whole Human Genome Microarrays containing 19,596 human genes. In addition to already described up-regulated mRNAs in cholesteatoma, such as MMP9, DEFB2 and KRT19, we identified 3558 new cholesteatoma-related transcripts. 811 genes appear to be significantly differentially up-regulated in cholesteatoma. 334 genes were down-regulated more than 2-fold. Significantly regulated genes with protein metabolism activity include matrix metalloproteinases as well as PI3, SERPINB3 and SERPINB4. Genes like SPP1, KRT6B, PRPH, SPRR1B and LAMC2 are known as genes with cell growth and/or maintenance activity. Transport activity genes and signal transduction genes are LCN2, GJB2 and CEACAM6. Three cell communication genes were identified; one CDH19 and two from the S100 family.
This study demonstrates that the expression profile of cholesteatoma is similar to a metastatic tumour and chronically inflamed tissue. Based on the investigated profiles we present novel protein-protein interaction and signal transduction networks, which include cholesteatoma-regulated transcripts and may be of great value for drug targeting and therapy development. |
| doi_str_mv | 10.1371/journal.pone.0052718 |
| format | Article |
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In this study, we investigated differentially expressed genes in human cholesteatomas in comparison to regular auditory canal skin using Whole Human Genome Microarrays containing 19,596 human genes. In addition to already described up-regulated mRNAs in cholesteatoma, such as MMP9, DEFB2 and KRT19, we identified 3558 new cholesteatoma-related transcripts. 811 genes appear to be significantly differentially up-regulated in cholesteatoma. 334 genes were down-regulated more than 2-fold. Significantly regulated genes with protein metabolism activity include matrix metalloproteinases as well as PI3, SERPINB3 and SERPINB4. Genes like SPP1, KRT6B, PRPH, SPRR1B and LAMC2 are known as genes with cell growth and/or maintenance activity. Transport activity genes and signal transduction genes are LCN2, GJB2 and CEACAM6. Three cell communication genes were identified; one CDH19 and two from the S100 family.
This study demonstrates that the expression profile of cholesteatoma is similar to a metastatic tumour and chronically inflamed tissue. Based on the investigated profiles we present novel protein-protein interaction and signal transduction networks, which include cholesteatoma-regulated transcripts and may be of great value for drug targeting and therapy development.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0052718</identifier><identifier>PMID: 23285167</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Auditory defects ; Bioinformatics ; Biology ; Bone loss ; Cell interactions ; Cellular signal transduction ; Cholesteatoma ; Cholesteatoma, Middle Ear - genetics ; Cholesteatoma, Middle Ear - metabolism ; Cholesteatoma, Middle Ear - pathology ; Cluster Analysis ; Computational Biology - methods ; Connexins ; Disease transmission ; DNA microarrays ; Ear ; Ear canal ; Eardrum ; Gelatinase B ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation ; Genes ; Genomes ; Genomics ; Health aspects ; Hearing loss ; Humans ; Infection ; Infections ; Inflammation ; Keratins - genetics ; Keratins - metabolism ; Matrix metalloproteinases ; Medicine ; Melanoma ; Meningitis ; Metabolism ; Metastases ; Middle ear ; Neurosciences ; Otolaryngology ; Paralysis ; Pathogenesis ; Protein folding ; Protein interaction ; Protein Interaction Mapping ; Protein Interaction Maps ; Protein metabolism ; Protein turnover ; Protein-protein interactions ; Proteins ; Reproducibility of Results ; RNA polymerase ; Signal Transduction ; Skin ; Skin cancer ; Surgery ; Temporal bone ; Transcriptome ; Transduction ; Tumors ; Vertigo</subject><ispartof>PloS one, 2012-12, Vol.7 (12), p.e52718-e52718</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Klenke et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Klenke et al 2012 Klenke et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-fb827f13eabe51cdbd5c33b92e3678d6aeecd0df1624718b57b5ede7f641c4d23</citedby><cites>FETCH-LOGICAL-c758t-fb827f13eabe51cdbd5c33b92e3678d6aeecd0df1624718b57b5ede7f641c4d23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527606/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527606/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23285167$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Chuang, Eric Y.</contributor><creatorcontrib>Klenke, Christin</creatorcontrib><creatorcontrib>Janowski, Sebastian</creatorcontrib><creatorcontrib>Borck, Daniela</creatorcontrib><creatorcontrib>Widera, Darius</creatorcontrib><creatorcontrib>Ebmeyer, Jörg</creatorcontrib><creatorcontrib>Kalinowski, Jörn</creatorcontrib><creatorcontrib>Leichtle, Anke</creatorcontrib><creatorcontrib>Hofestädt, Ralf</creatorcontrib><creatorcontrib>Upile, Tahwinder</creatorcontrib><creatorcontrib>Kaltschmidt, Christian</creatorcontrib><creatorcontrib>Kaltschmidt, Barbara</creatorcontrib><creatorcontrib>Sudhoff, Holger</creatorcontrib><title>Identification of novel cholesteatoma-related gene expression signatures using full-genome microarrays</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Cholesteatoma is a gradually expanding destructive epithelial lesion within the middle ear. It can cause extensive local tissue destruction in the temporal bone and can initially lead to the development of conductive hearing loss via ossicular erosion. As the disease progresses, sensorineural hearing loss, vertigo or facial palsy may occur. Cholesteatoma may promote the spread of infection through the tegmen of the middle ear and cause meningitis or intracranial infections with abscess formation. It must, therefore, be considered as a potentially life-threatening middle ear disease.
In this study, we investigated differentially expressed genes in human cholesteatomas in comparison to regular auditory canal skin using Whole Human Genome Microarrays containing 19,596 human genes. In addition to already described up-regulated mRNAs in cholesteatoma, such as MMP9, DEFB2 and KRT19, we identified 3558 new cholesteatoma-related transcripts. 811 genes appear to be significantly differentially up-regulated in cholesteatoma. 334 genes were down-regulated more than 2-fold. Significantly regulated genes with protein metabolism activity include matrix metalloproteinases as well as PI3, SERPINB3 and SERPINB4. Genes like SPP1, KRT6B, PRPH, SPRR1B and LAMC2 are known as genes with cell growth and/or maintenance activity. Transport activity genes and signal transduction genes are LCN2, GJB2 and CEACAM6. Three cell communication genes were identified; one CDH19 and two from the S100 family.
This study demonstrates that the expression profile of cholesteatoma is similar to a metastatic tumour and chronically inflamed tissue. Based on the investigated profiles we present novel protein-protein interaction and signal transduction networks, which include cholesteatoma-regulated transcripts and may be of great value for drug targeting and therapy development.</description><subject>Auditory defects</subject><subject>Bioinformatics</subject><subject>Biology</subject><subject>Bone loss</subject><subject>Cell interactions</subject><subject>Cellular signal transduction</subject><subject>Cholesteatoma</subject><subject>Cholesteatoma, Middle Ear - genetics</subject><subject>Cholesteatoma, Middle Ear - metabolism</subject><subject>Cholesteatoma, Middle Ear - pathology</subject><subject>Cluster Analysis</subject><subject>Computational Biology - methods</subject><subject>Connexins</subject><subject>Disease transmission</subject><subject>DNA microarrays</subject><subject>Ear</subject><subject>Ear canal</subject><subject>Eardrum</subject><subject>Gelatinase B</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Health aspects</subject><subject>Hearing loss</subject><subject>Humans</subject><subject>Infection</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Keratins - genetics</subject><subject>Keratins - metabolism</subject><subject>Matrix metalloproteinases</subject><subject>Medicine</subject><subject>Melanoma</subject><subject>Meningitis</subject><subject>Metabolism</subject><subject>Metastases</subject><subject>Middle ear</subject><subject>Neurosciences</subject><subject>Otolaryngology</subject><subject>Paralysis</subject><subject>Pathogenesis</subject><subject>Protein folding</subject><subject>Protein interaction</subject><subject>Protein Interaction Mapping</subject><subject>Protein Interaction Maps</subject><subject>Protein metabolism</subject><subject>Protein turnover</subject><subject>Protein-protein interactions</subject><subject>Proteins</subject><subject>Reproducibility of Results</subject><subject>RNA polymerase</subject><subject>Signal Transduction</subject><subject>Skin</subject><subject>Skin cancer</subject><subject>Surgery</subject><subject>Temporal bone</subject><subject>Transcriptome</subject><subject>Transduction</subject><subject>Tumors</subject><subject>Vertigo</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tq3DAQhk1padK0b1BaQ6G0F95a1sl7Uwihh4VAoKdbIUsjrxbZ2kp2SN6-ctcJ65KL4gvZ0je_PP_MZNlLVK4Q5ujDzo-hl2619z2sypJWHNWPslO0xlXBqhI_Pno_yZ7FuEsQrhl7mp1UuKopYvw0MxsN_WCNVXKwvs-9yXt_DS5XW-8gDiAH38kigJMD6LyFHnK42QeIccKjbXs5jOkzH6Pt29yMzhWJ8h3knVXByxDkbXyePTHSRXgxr2fZz8-fflx8LS6vvmwuzi8LxWk9FKapK24QBtkARUo3miqMm3UFmPFaMwmgdKkNYhVJ6TaUNxQ0cMMIUkRX-Cx7fdDdOx_FbFEUCCd31jUtSSI2B0J7uRP7YDsZboWXVvzd8KEVMgxWORBcKsYbRgjWnGCJGsPWCpnGEE2oUixpfZxvG5sOtEpOBukWosuT3m5F668FTtVi5STwbhYI_veY7BadjQqckz34Mf13xTFilOE6oW_-QR_ObqZamRKwvfHpXjWJinPCeUlrUtNErR6g0qMh1Sz1k7FpfxHwfhGQmAFuhlaOMYrN92__z179WrJvj9gtSDdso3fj1IpxCZIDmDoqxgDm3mRUimkc7twQ0ziIeRxS2KvjAt0H3fU__gOlRAhb</recordid><startdate>20121220</startdate><enddate>20121220</enddate><creator>Klenke, 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Sebastian</au><au>Borck, Daniela</au><au>Widera, Darius</au><au>Ebmeyer, Jörg</au><au>Kalinowski, Jörn</au><au>Leichtle, Anke</au><au>Hofestädt, Ralf</au><au>Upile, Tahwinder</au><au>Kaltschmidt, Christian</au><au>Kaltschmidt, Barbara</au><au>Sudhoff, Holger</au><au>Chuang, Eric Y.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of novel cholesteatoma-related gene expression signatures using full-genome microarrays</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-12-20</date><risdate>2012</risdate><volume>7</volume><issue>12</issue><spage>e52718</spage><epage>e52718</epage><pages>e52718-e52718</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Cholesteatoma is a gradually expanding destructive epithelial lesion within the middle ear. It can cause extensive local tissue destruction in the temporal bone and can initially lead to the development of conductive hearing loss via ossicular erosion. As the disease progresses, sensorineural hearing loss, vertigo or facial palsy may occur. Cholesteatoma may promote the spread of infection through the tegmen of the middle ear and cause meningitis or intracranial infections with abscess formation. It must, therefore, be considered as a potentially life-threatening middle ear disease.
In this study, we investigated differentially expressed genes in human cholesteatomas in comparison to regular auditory canal skin using Whole Human Genome Microarrays containing 19,596 human genes. In addition to already described up-regulated mRNAs in cholesteatoma, such as MMP9, DEFB2 and KRT19, we identified 3558 new cholesteatoma-related transcripts. 811 genes appear to be significantly differentially up-regulated in cholesteatoma. 334 genes were down-regulated more than 2-fold. Significantly regulated genes with protein metabolism activity include matrix metalloproteinases as well as PI3, SERPINB3 and SERPINB4. Genes like SPP1, KRT6B, PRPH, SPRR1B and LAMC2 are known as genes with cell growth and/or maintenance activity. Transport activity genes and signal transduction genes are LCN2, GJB2 and CEACAM6. Three cell communication genes were identified; one CDH19 and two from the S100 family.
This study demonstrates that the expression profile of cholesteatoma is similar to a metastatic tumour and chronically inflamed tissue. Based on the investigated profiles we present novel protein-protein interaction and signal transduction networks, which include cholesteatoma-regulated transcripts and may be of great value for drug targeting and therapy development.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23285167</pmid><doi>10.1371/journal.pone.0052718</doi><tpages>e52718</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-12, Vol.7 (12), p.e52718-e52718 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1327198504 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Auditory defects Bioinformatics Biology Bone loss Cell interactions Cellular signal transduction Cholesteatoma Cholesteatoma, Middle Ear - genetics Cholesteatoma, Middle Ear - metabolism Cholesteatoma, Middle Ear - pathology Cluster Analysis Computational Biology - methods Connexins Disease transmission DNA microarrays Ear Ear canal Eardrum Gelatinase B Gene expression Gene Expression Profiling Gene Expression Regulation Genes Genomes Genomics Health aspects Hearing loss Humans Infection Infections Inflammation Keratins - genetics Keratins - metabolism Matrix metalloproteinases Medicine Melanoma Meningitis Metabolism Metastases Middle ear Neurosciences Otolaryngology Paralysis Pathogenesis Protein folding Protein interaction Protein Interaction Mapping Protein Interaction Maps Protein metabolism Protein turnover Protein-protein interactions Proteins Reproducibility of Results RNA polymerase Signal Transduction Skin Skin cancer Surgery Temporal bone Transcriptome Transduction Tumors Vertigo |
| title | Identification of novel cholesteatoma-related gene expression signatures using full-genome microarrays |
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