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Identification of 9 Genes Differentially Expressed in Head and Neck Squamous Cell Carcinoma
Hernan E. Gonzalez, MD, PhD;
Manu Gujrati, MD;
Mitchell Frederick, PhD;
Ying Henderson, MD, PhD;
Jayakumar Arumugam, PhD;
Paul W. Spring, MD;
Kenji Mitsudo, DDS, PhD;
Hyung-Woo Kim, MS;
Gary L. Clayman, DDS, MD
Arch Otolaryngol Head Neck Surg. 2003;129:754-759.
Background Current treatment modalities in squamous cell carcinoma of the head and neck have failed to improve survival. Advances in the discovery of novel biomarkers and targets for therapy are necessary.
Design Differential display and microarray analysis were used to identify differences in gene expression between squamous carcinoma and matched nonmalignant biopsy specimens. Differences in gene expression found in vivo were also tested in vitro by comparing primary cultured normal oral epithelium with head and neck squamous cell carcinoma (HNSCC) cell lines. Results were confirmed by relative reverse transcriptase–polymerase chain reaction and immunohistochemical analysis.
Results In tumors, microarray analysis showed down-regulation of calgranulin B (CAGB), CD24, lymphoepithelial Kazal-type–related inhibitor (LEKTI), zinc finger protein (ZNF-185), transglutaminase-3 (TGM3), and the ETS homologous factor (EHF). In addition, differential display revealed down-regulation of headpin. In contrast, periostin and the human homologue of the Drosophila white gene (ABCG1) were found to be up-regulated by microarray analysis and differential display, respectively. In HNSCC cell lines, LEKTI, ZNF-185, TGM3, headpin, and ABCG1 showed an expression pattern similar to that observed in tumor specimens. Periostin showed an opposite expression pattern in cell lines compared with that of tumor specimens. No consistent pattern of expression was found for CAGB, CD24, and EHF in cell lines. Immunohistochemical analysis revealed that the expression of headpin in nonmalignant mucosa was undetectable in tumors.
Conclusion Using differential display and microarray analysis, we have identified and confirmed the differential expression of 9 genes in HNSCC. Work is in progress to determine the biological significance of these genes and their potential as biomarkers or targets for therapy.
From the Departments of Head and Neck Surgery (Drs Gonzalez, Gujrati, Frederick, Henderson, Arumugam, Mitsudo, and Clayman) and Biostatistics (Mr Kim), University of Texas M. D. Anderson Cancer Center, Houston; and the Division of Otolaryngology and Head and Neck Surgery, University of Kentucky Chandler Medical Center, Lexington (Dr Spring). The authors have no relevant financial interest in this article.
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