Expression Profile of Angiogenesis Related Genes in Head and Neck Squamous Cell Carcinoma

Abstract

Objectives: The molecular patterns of tumorigenesis of head and neck squamous cell carcinoma are mostly unknown to date. The concept of this investigation was to expose a genetic fingerprint of angiogenesis in HNSCC with special regard to VEGF as the outstanding mediator of neo-angiogenesis. Material and Methods: A panel of significant transcriptional alterations of VEGF related genes in 83 cancer samples compared to healthy mucosa with microarray technique was established. RT-PCR and immunohistochemistry were performed to confirm the microarray results. Results: In four selected marker genes (VEGFA, RAC2, IL8, PLA2G10) we detected a highly significant transcriptional alteration; three of the genes (VEGFA, RAC2, IL8) showed up-regulation in 88% to 100% of the samples, PLA2G10 down-regulation in 99% of the analyzed tissue samples. Additionally a significant transcription alteration in angio-miRNAs was detected: miR-21 and miR-31 were over-expressed in upto 87% and upto 89% respectively in the analyzed samples. MiR-20a, miR-126, miR-378, miR-17, miR-19a, miR-27b and miR let-7f were down-regulated in 83% to 95% of the specimens. A specific pattern subjected to the different tumor types could not be verified. Conclusion: An expression profile of VEGF related genes was established and selective angio-miRNAs were identified as potential biomarkers on the basis of 83 HNSCC samples. Identification of new relevant oncogenes and insight into the process of tumor vasculogenesis with a highly sensitive method opens new vistas in cancer biology.