title: Proteomic analysis reveals successive aberrations in protein expression from healthy mucosa to invasive head and neck cancer.
abstract: Development of head and neck squamous cell carcinoma (HNSCC) is a multistep process and in many cases involves a phenomenon coined 'field cancerization'. In order to identify changes in protein expression occurring at different stages of tumorigenesis and field cancerization, we analysed 113 HNSCCs and 73 healthy, 99 tumor-distant and 18 tumor-adjacent squamous mucosae by SELDI-TOF-MS on IMAC30 ProteinChip Arrays. Forty-eight protein peaks were differentially expressed between healthy mucosa and HNSCC. Calgizarrin (S100A11), the Cystein proteinase inhibitor Cystatin A, Acyl-CoA-binding protein, Stratifin (14-3-3 sigma), Histone H4, alpha- and beta-Hemoglobin, a C-terminal fragment of beta-hemoglobin and the alpha-defensins 1-3 were identified by mass spectrometry. The alpha-defensins showed various alterations in expression as validated by immunohistochemistry (IHC). Supervised prediction analysis revealed excellent classification of healthy mucosa (94.5% correctly classified) and tumor samples (92.9% correctly classified). Application of this classifier to the tumor-adjacent and tumor-distant mucosa samples disclosed dramatic changes: only 59.6% of the tumor-distant biopsies were classified as normal, 27.3% were predicted as aberrant or HNSCC. Strikingly, 72% of the tumor-adjacent mucosae were predicted as aberrant. These data provide evidence for the existence of genetically altered fields with inconspicuous histology. Comparison of the protein profiles in the tumor-distant-samples with clinical outcome of 32 patients revealed a significant association between aberrant profiles with tumor relapse events (P=0.018; Fisher's exact test, two-tailed). We conclude that proteomic profiling in conjunction with protein identification greatly outperforms histopathological diagnosis and may have significant predictive power for clinical outcome and personalized risk assessment.
authors.affiliation: Molecular Biology Laboratory, Department of Otolaryngology, Head & Neck Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Roesch-Ely
authors.forename: M
authors.initials: M
authors.lastname: Nees
authors.forename: S
authors.initials: S
authors.lastname: Karsai
authors.forename: A
authors.initials: A
authors.lastname: Ruess
authors.forename: R
authors.initials: R
authors.lastname: Bogumil
authors.forename: U
authors.initials: U
authors.lastname: Warnken
authors.forename: M
authors.initials: M
authors.lastname: Schnölzer
authors.forename: A
authors.initials: A
authors.lastname: Dietz
authors.forename: P K
authors.initials: PK
authors.lastname: Plinkert
authors.forename: C
authors.initials: C
authors.lastname: Hofele
authors.forename: F X
authors.initials: FX
authors.lastname: Bosch
mesh_terms: D000595:Amino Acid Sequence; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D009363:Neoplasm Proteins