Divergent Gene Expression Profiles In Hpv-Positive And Hpv-Negative Head And Neck Squamous Cell Carcinomas

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Up to 60% of oropharyngeal cancers and 25% of head and neck squamous cell carcinomas (HNSCC) are due to high-risk Human Papillomavirus (HPV), primarily HPV16. Differences in risk factors, age of presentation and clinical behavior of these tumors indicate that HPV+ and HPV- tumors develop with different molecular mechanisms and are biologically distinct. To further investigate the molecular characteristics of these tumors, we compared the gene expression profiles of three HPV- and four HPV+ HNSCC specimens, obtained from the Medical University of South Carolina ENT/Head and Neck Surgery clinic. All HPV+ tumors were positive for HPV16 and expressed E7, as documented by real-time RT/PCR using tumor-derived RNA. Gene expression profiles were determined on Agilent 4x44K human oligonucleotide microarrays. Identification of differentially expressed genes (>2-fold change, p<0.05) and pathway analysis were performed using GeneSifter Software (Geospiza). Overall, 125 genes were up-regulated and 223 were down-regulated in HPV+ in comparison with HPV- tumors. Gene Ontology analysis of the dataset revealed that pathways related to cell cycle control, mitotic checkpoint, regulation of cell proliferation, programmed cell death and DNA metabolism were heavily affected in HPV+ tumors, while pathways affected in HPV- tumors included regulation of cell motility and migration, angiogenesis and integrin-mediated signaling. We confirmed by Real-Time RT/PCR the differential expression of a panel of genes of interest on these samples and several additional HNSCC specimens, and then we extended our follow-up analysis to specimens from over 30 new cases of HNSCC. Among the genes we targeted for follow-up is the MET oncogene, which encodes the hepatocyte growth factor/scatter factor receptor. MET is overexpressed about 5-fold in HPV- tumors, in comparison with HPV+ tumors actively expressing E7. The MET product, which controls growth, invasion and metastasis in cancer cells, has been recently proposed as a new therapeutic target for HNSCC. Supported by grant #P20MD001770 from the NIH/NIMHD. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5110. doi:1538-7445.AM2012-5110