title: Identification of altered protein abundances in cholesteatoma matrix via mass spectrometry-based proteomic analysis.
abstract: BACKGROUND
  Cholesteatoma are cyst-like structures lined with a matrix of differentiated squamous epithelium overlying connective tissue. Although epithelium normally exhibits self-limited growth, cholesteatoma matrix erodes mucosa and bone suggesting changes in matrix protein constituents that permit destructive behaviour. Differential proteomic studies can measure and compare the cholesteatoma proteome to normal tissues, revealing protein alterations that may propagate the destructive process.
  
  
  METHODS
  Human cholesteatoma matrix, cholesteatoma-involved ossicles, and normal middle ear mucosa, post-auricular skin, and non-involved ossicles were harvested. These tissues were subjected to multiplex peptide labeling followed by liquid chromatography and tandem mass spectrometry analysis. Relative protein abundances were compared and evaluated for ontologic function and putative involvement in cholesteatoma.
  
  
  RESULTS
  Our methodology detected 10 764 peptides constituting 1662 unique proteins at 95 % confidence or greater. Twenty-nine candidate proteins were identified in soft tissue analysis, with 29 additional proteins showing altered abundances in bone samples. Ontologic functions and known relevance to cholesteatoma are discussed, with several candidates highlighted for their roles in epithelial integrity, evasion of apoptosis, and immunologic function.
  
  
  CONCLUSIONS
  This study produced an extensive cholesteatoma proteome and identified 58 proteins with altered abundances contributing to disease pathopathysiology. As well, potential biomarkers of residual disease were highlighted. Further investigation into these proteins may provide useful options for novel therapeutics or monitoring disease status.
authors.affiliation: Section of Otolaryngology - Head & Neck Surgery, Department of Surgery, University of Calgary, Calgary, Foothills Medical Centre, 1403 - 29 Street NW, Calgary, AB, T2N 2T9, Canada.
authors.forename: Derrick R
authors.initials: DR
authors.lastname: Randall
authors.affiliation: Section of Otolaryngology - Head & Neck Surgery, Department of Surgery, University of Calgary, Calgary, Foothills Medical Centre, 1403 - 29 Street NW, Calgary, AB, T2N 2T9, Canada.
authors.forename: Phillip S
authors.initials: PS
authors.lastname: Park
authors.affiliation: Section of Otolaryngology - Head & Neck Surgery, Department of Surgery, University of Calgary, Calgary, Foothills Medical Centre, 1403 - 29 Street NW, Calgary, AB, T2N 2T9, Canada. justin.chau@gmail.com.
authors.forename: Justin K
authors.initials: JK
authors.lastname: Chau
mesh_terms: D002454:Cell Differentiation; D018424:Cholesteatoma, Middle Ear / Q000175:diagnosis / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D006801:Humans; D013058:Mass Spectrometry; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*
chemical_list: D020543:Proteome