Overexpression of antiangiogenic vascular endothelial growth factor isoform and splicing regulatory factors in oral, larynx and pharynx squamous cell carcinoma

• Grant number: 17/16598-3
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: September 01, 2017
• End date: April 30, 2018
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Eny Maria Goloni Bertollo
• Grantee: Eny Maria Goloni Bertollo
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil

Abstract

Background: Overexpression of proangiogenic vascular endothelial growth factor A family VEGFAxxx is associated with tumor growth and metastasis. The role of the alternatively spliced antiangiogenic family VEGFAxxxb is poorly investigated in head and neck squamous cell carcinoma (HNSCC). The antiangiogenic isoform binds to bevacizumab and the expression level in HNSCC could influence the treatment response and the progression-free survival of the patients. In this study, we investigated the relative expression of VEGFAxxx and VEGFA165b isoforms and splicing regulatory factors genes in HNSCC. Methods: VEGFAxxx, VEGFA165b, SRSF6, SRSF5, SRSF1 and SRPK1 gene expression was quantified by quantitative real time PCR of 53 tissues extracted from surgery of HNSCC patients. Protein expression was evaluated by immunohistochemistry. Results: VEGFAxxx and VEGFA165b were overexpressed in HNSCC. Protein expression confirmed these results. VEGFA isoforms have differential expression according to the head and neck anatomical sites. VEGFAxxx was overexpressed in pharynx tumors and VEGFA165b isoform was up regulated in oral tumors. VEGFA165b isoform was positively correlated with expression of the splicing regulatory genes SRSF1, SRSF6 and SRSF5. Conclusions: We concluded that VEGFAxxx and VEGFA165b isoforms are overexpressed in HNSCC and the splicing regulatory factors SRSF1, SRSF6, SRSF5 and SRPK1 may contribute to the alternative splicing of VEGFA gene in this tumor type. The findings on the differential expression of the antiangiogenic isoform in HNSCC could direct to most effective therapeutic strategies for the management of these tumors. (AU)