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

Oncogene volume 26, pages 54–64 (2007)Cite this article

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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Acknowledgements

Grant support: We specially thank the CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for financial support to M Roesch-Ely. We greatly appreciate the help from our medical staff in collecting and processing the tissue specimens, and Dr Christa Flechtenmacher, Pathologisches Institut der Universität Heidelberg, for histopathological assessment and fruitful discusssions. We thank Antje Schuhmann and Nataly Henfling for excellent technical support. Equipment was financed via the ‘Hochschulbau-Förderungsgesetz’. This study was in part supported by the ‘Forschungsförderungsprogramm der Medizinischen Fakultät Heidelberg’, Grant No. 007 and a grant from the National Genome Research Network to MS (Förderkennzeichen 01GS0460).

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Author notes

  1. M Nees

    Present address: VTT Biomedical Research Center, Itäinen Pitkäkatu 4A, 20521, Turku, Finland

  2. M Roesch-Ely and M Nees: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Otolaryngology, Molecular Biology Laboratory, Head & Neck Surgery, University of Heidelberg, Heidelberg, Germany

    M Roesch-Ely, M Nees, S Karsai, A Ruess, A Dietz, P K Plinkert & F X Bosch

  2. Ciphergen Biosystems GmbH, Berlin-Hennigsdorf, Germany

    R Bogumil

  3. Protein Analysis Facility, German Cancer Research Center, Heidelberg, Germany

    U Warnken & M Schnölzer

  4. Ear-Nose and Throat Department, University of Leipzig, Liebigstrasse, Leipzig, Germany

    A Dietz

  5. Department of Oral and Maxillofacial Surgery, University of Heidelberg, Heidelberg, Germany

    C Hofele

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Correspondence to F X Bosch.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Roesch-Ely, M., Nees, M., Karsai, S. et al. Proteomic analysis reveals successive aberrations in protein expression from healthy mucosa to invasive head and neck cancer. Oncogene 26, 54–64 (2007). https://doi.org/10.1038/sj.onc.1209770

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