title: Comparative proteome analysis to explore p53 pathway disruption in head and neck carcinogenesis.
abstract: The 5-year-survival rate of head and neck squamous cell carcinoma (HNSCC) has been only moderately improved over the last few decades. HNSCC develops in precursor fields of genetically altered mucosal cells, typically characterized by p53 pathway disruption, that mostly do not give any clinical symptoms. Patients present therefore often with invasive carcinomas in an advanced stage. After tumor resection, part of these fields frequently stays behind unnoticed, causing secondary tumors. Identification of these precursor fields would allow screening and early detection of both primary and secondary tumors. Our aim was to identify differential proteins related to p53 dysfunction. These proteins may serve as valuable biomarkers that can predict the presence of a precursor field. We used a squamous cell model for p53 inactivation, which was analyzed by 2D-DIGE and LC-MS/MS. This approach enabled us to identify a set of 74 proteins that were differentially expressed in cells with normal versus disrupted p53 function. For six proteins the major changes in expression were verified with immunohistochemical staining. The most promising result was the identification of peroxiredoxin-1 which allowed immunohistochemical discrimination between normal epithelium and precursor field tissue with a TP53 mutation.
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
authors.forename: Tieneke B M
authors.initials: TB
authors.lastname: Schaaij-Visser
authors.forename: Ruud H
authors.initials: RH
authors.lastname: Brakenhoff
authors.forename: Jeroen W A
authors.initials: JW
authors.lastname: Jansen
authors.forename: Martina C
authors.initials: MC
authors.lastname: O'Flaherty
authors.forename: Serge J
authors.initials: SJ
authors.lastname: Smeets
authors.forename: Albert J R
authors.initials: AJ
authors.lastname: Heck
authors.forename: Monique
authors.initials: M
authors.lastname: Slijper
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015603:Keratinocytes / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D020543:Proteome; D040901:Proteomics / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; D020543:Proteome; D016159:Tumor Suppressor Protein p53