Overexpression of Antiangiogenic Vascular Endothelial Growth Factor Isoform and Splicing Regulatory Factors in Oral, Laryngeal and Pharyngeal Squamous Cell Carcinomas

Biselli-Chicote, Patrícia Matos; Biselli, Joice; Cunha, Bianca; Castro, Rodrigo; Maniglia, José Victor; Neto, Dalísio De Santi; Tajara, Eloiza Helena; Góis Filho, José Franscisco De; Fukuyama, Erica Erina; Pavarino, Érika Cristina; Goloni-Bertollo, Eny Maria

doi:10.22034/APJCP.2017.18.8.2171

Overexpression of Antiangiogenic Vascular Endothelial Growth Factor Isoform and Splicing Regulatory Factors in Oral, Laryngeal and Pharyngeal Squamous Cell Carcinomas

Document Type : Research Articles

Authors

¹ Genetics and Molecular Biology Research Unit, Sao Jose do Rio Preto Medical School, Sao Jose do Rio Preto, Brazil.

² Laboratory of Molecular Markers and Medical Bioinformatics, Sao Jose do Rio Preto Medical School, Sao Jose do Rio Preto, Brazil.

³ Department of Otolaryngology and Head and Neck Surgery, São José do Rio Preto Medical School, Sao Jose do Rio Preto, Brazil.

⁴ Department of Pathology, Hospital de Base, Sao Jose do Rio Preto, São Paulo, Brazil.

⁵ Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil.

⁶ Department of Head and Neck Surgery, Arnaldo Vieira de Carvalho Cancer Institute, Sao Paulo, Brazil.

10.22034/APJCP.2017.18.8.2171

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 carcinomas (HNSCCs). The antiangiogenic isoform binds to bevacizumab and its expression level could influence the treatment response and progression-free survival. In this study, the relative expression of VEGFAxxx and VEGFA165b isoforms and splicing regulatory factors genes was investigated in a series of HNSCCs. Methods: VEGFAxxx, VEGFA165b, SRSF6, SRSF5, SRSF1 and SRPK1 gene expression was quantified by quantitative real time PCR in 53 tissue samples obtained by surgery from HNSCC patients. Protein expression was evaluated by immunohistochemistry. Results: VEGFAxxx and VEGFA165b were overexpressed in HNSCCs. Elevated protein expression was also confirmed. However, VEGFA isoforms demonstrated differential expression according to anatomical sites. VEGFAxxx was overexpressed in pharyngeal tumors while the VEGFA165b isoform was up-regulated in oral tumors. The VEGFA165b isoform was also positively correlated with expression of the splicing regulatory genes SRSF1, SRSF6 and SRSF5. Conclusions: We concluded that VEGFAxxx and VEGFA165b isoforms are overexpressed in HNSCCs and the splicing regulatory factors SRSF1, SRSF6, SRSF5 and SRPK1 may contribute to alternative splicing of the VEGFA gene. The findings for the differential expression of the antiangiogenic isoform in HNSCCs could facilitate effective therapeutic strategies for the management of these tumors.

Keywords