2D-DIGE Proteomic Characterization of Head and Neck Squamous Cell Carcinoma

Overview

Journal Otolaryngol Head Neck Surg

Publisher Wiley

Specialties General Surgery
Otorhinolaryngology

Date 2009 Oct 29

PMID 19861202

Citations 3

Authors

Mark A Merkley

Paul M Weinberger

Lana L Jackson

Robert H Podolsky

Jeffrey R Lee

William S Dynan

Affiliations

Soon will be listed here.

Abstract

Objective: Identify proteins that are differentially expressed between head and neck squamous cell cancer (HNSCC) and patient-matched normal adjacent tissue, and validate findings in a separate patient cohort.

Study Design: Cross-sectional study of surgical specimens.

Setting: Tertiary care academic medical center.

Subjects And Methods: Laser capture microdissection and two-dimensional difference gel electrophoresis were used previously to establish proteomic profiles for tumor and normal adjacent tissue from 14 patients. Here, significance analysis of microarray was used to rank candidate biomarkers. Spots meeting statistical and biological criteria of significance were analyzed by liquid chromatography and tandem mass spectrometry to obtain protein identifications. The expression pattern of the highest-ranked candidate biomarker (cornulin) was validated in a larger, independent patient cohort (n = 68) by immunohistochemical staining of a tissue microarray.

Results: Of 732 spots, 117 (15.9%) met criteria for significance. Identities were obtained for 39 spots, representing 17 different proteins. Four proteins were novel in the context of HNSCC: glutathione synthetase, which was upregulated; and cornulin (squamous epithelial heat shock protein 53), guanylate binding protein 6, and heat shock 70 kDa protein 5 (glucose-regulated protein, 78 kDa), which were downregulated. Cornulin functions in the stress response in normal squamous epithelium, and reduced expression has been proposed as a marker of susceptibility to laryngopharyngeal reflux and other stressors. Loss of cornulin expression was confirmed in an independent HNSCC patient cohort (P < 0.001).

Conclusions: Downregulation of cornulin is a prominent feature of the molecular signature of HNSCC identified by comparative proteomics. Cornulin may represent a link between HNSCC and other pathologies arising in stratified squamous epithelium.

Citing Articles

Protein Profiling in Human Papillomavirus-Associated Cervical Carcinogenesis: Cornulin as a Biomarker for Disease Progression.

Kumarasamy G, Ismail M, Tuan Sharif S, Desire C, Mittal P, Hoffmann P Curr Issues Mol Biol. 2023; 45(4):3603-3627.

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Microproteomics: quantitative proteomic profiling of small numbers of laser-captured cells.

Roulhac P, Ward J, Thompson J, Soderblom E, Silva M, Moseley 3rd M Cold Spring Harb Protoc. 2011; 2011(2):pdb.prot5573.

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New advances in molecular approaches to head and neck squamous cell carcinoma.

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