title: Identification of novel cholesteatoma-related gene expression signatures using full-genome microarrays.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Klinikum Bielefeld, Bielefeld, Germany. christin.zander@klinikumbielefeld.de
authors.forename: Christin
authors.initials: C
authors.lastname: Klenke
authors.forename: Sebastian
authors.initials: S
authors.lastname: Janowski
authors.forename: Daniela
authors.initials: D
authors.lastname: Borck
authors.forename: Darius
authors.initials: D
authors.lastname: Widera
authors.forename: Jörg
authors.initials: J
authors.lastname: Ebmeyer
authors.forename: Jörn
authors.initials: J
authors.lastname: Kalinowski
authors.forename: Anke
authors.initials: A
authors.lastname: Leichtle
authors.forename: Ralf
authors.initials: R
authors.lastname: Hofestädt
authors.forename: Tahwinder
authors.initials: T
authors.lastname: Upile
authors.forename: Christian
authors.initials: C
authors.lastname: Kaltschmidt
authors.forename: Barbara
authors.initials: B
authors.lastname: Kaltschmidt
authors.forename: Holger
authors.initials: H
authors.lastname: Sudhoff
mesh_terms: D018424:Cholesteatoma, Middle Ear / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D000072259:Connexin 26; D017630:Connexins; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D015203:Reproducibility of Results; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D007633:Keratins