Proteomic analysis reveals successive aberrations in protein expression from healthy mucosa to invasive head and neck cancer

M. Roesch-Ely, Matthias Nees, S. Karsai, A. Ruess, R. Bogumi, U. Warnken, M. Schnölzer, A. Dietz, P. K. Plinkert, C. Hofele, F. X. Bosch

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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, α- and β-Hemoglobin, a C-terminal fragment of β-hemoglobin and the α-defensins 1–3 were identified by mass spectrometry. The α-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.
Original languageEnglish
Pages (from-to)54-64
JournalOncogene
Volume26
Issue number1
DOIs
Publication statusPublished - 2007
MoE publication typeA1 Journal article-refereed

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Head and Neck Neoplasms
Proteomics
Mucous Membrane
Neoplasms
Proteins
Defensins
Cystatin A
Diazepam Binding Inhibitor
Hemoglobin C
14-3-3 Proteins
Protein Array Analysis
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Histones
Mass Spectrometry
Histology
Carcinogenesis
Hemoglobins
Peptide Hydrolases
Immunohistochemistry
Biopsy

Keywords

  • proteomics
  • SELDI-TOF-MS
  • HNSCC
  • field cancerization
  • protein biomarkers

Cite this

Roesch-Ely, M., Nees, M., Karsai, S., Ruess, A., Bogumi, R., Warnken, U., ... Bosch, F. X. (2007). Proteomic analysis reveals successive aberrations in protein expression from healthy mucosa to invasive head and neck cancer. Oncogene, 26(1), 54-64. https://doi.org/10.1038/sj.onc.1209770
Roesch-Ely, M. ; Nees, Matthias ; Karsai, S. ; Ruess, A. ; Bogumi, R. ; Warnken, U. ; Schnölzer, M. ; Dietz, A. ; Plinkert, P. K. ; Hofele, C. ; Bosch, F. X. / Proteomic analysis reveals successive aberrations in protein expression from healthy mucosa to invasive head and neck cancer. In: Oncogene. 2007 ; Vol. 26, No. 1. pp. 54-64.
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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, α- and β-Hemoglobin, a C-terminal fragment of β-hemoglobin and the α-defensins 1–3 were identified by mass spectrometry. The α-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.",
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Roesch-Ely, M, Nees, M, Karsai, S, Ruess, A, Bogumi, R, Warnken, U, Schnölzer, M, Dietz, A, Plinkert, PK, Hofele, C & Bosch, FX 2007, 'Proteomic analysis reveals successive aberrations in protein expression from healthy mucosa to invasive head and neck cancer', Oncogene, vol. 26, no. 1, pp. 54-64. https://doi.org/10.1038/sj.onc.1209770

Proteomic analysis reveals successive aberrations in protein expression from healthy mucosa to invasive head and neck cancer. / Roesch-Ely, M.; Nees, Matthias; Karsai, S.; Ruess, A.; Bogumi, R.; Warnken, U.; Schnölzer, M.; Dietz, A.; Plinkert, P. K.; Hofele, C.; Bosch, F. X.

In: Oncogene, Vol. 26, No. 1, 2007, p. 54-64.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Proteomic analysis reveals successive aberrations in protein expression from healthy mucosa to invasive head and neck cancer

AU - Roesch-Ely, M.

AU - Nees, Matthias

AU - Karsai, S.

AU - Ruess, A.

AU - Bogumi, R.

AU - Warnken, U.

AU - Schnölzer, M.

AU - Dietz, A.

AU - Plinkert, P. K.

AU - Hofele, C.

AU - Bosch, F. X.

PY - 2007

Y1 - 2007

N2 - 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, α- and β-Hemoglobin, a C-terminal fragment of β-hemoglobin and the α-defensins 1–3 were identified by mass spectrometry. The α-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.

AB - 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, α- and β-Hemoglobin, a C-terminal fragment of β-hemoglobin and the α-defensins 1–3 were identified by mass spectrometry. The α-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.

KW - proteomics

KW - SELDI-TOF-MS

KW - HNSCC

KW - field cancerization

KW - protein biomarkers

U2 - 10.1038/sj.onc.1209770

DO - 10.1038/sj.onc.1209770

M3 - Article

VL - 26

SP - 54

EP - 64

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 1

ER -