Genetic expression profiles and biologic pathway alterations in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is associated with considerable mortality and morbidity and is a major public health concern worldwide. To date, > 20 studies incorporating DNA microarray analyses have examined genomewide genetic expression changes associated with the development of HNSCC. The authors identified published reports of genetic expression profiles of HNSCC by Medline database search. They performed a review of the reports to identify genes that have been found repeatedly to exhibit substantially altered expression in HNSCC. Genes with altered expression were subsequently examined in the context of defined biologic systems with the use of GenMapp 2.0 pathway analysis software. Genes most commonly found to exhibit altered expression were those encoding for cytoskeletal and extracellular matrix proteins, inflammatory mediators, proteins involved in epidermal differentiation, and cell adhesion molecules. Results of GenMapp 2.0 analysis suggested global down-regulation of genes that encode for ribosomal proteins and enzymes in the cholesterol biosynthesis pathway; and up-regulation of genes that encode for matrix metalloproteinases and genes that bear on the inflammatory response. The review indicated that there are several genes and pathways that exhibit substantially altered expression in cancerous versus noncancerous states across studies. Further investigation into the genomic, proteomic, and functional consequences of these gene expression alterations may provide insight into the pathophysiology of HNSCC. Copyright 2005 American Cancer Society.