Farhan Mehedi
University Of Nottingham, United Kingdom.
Title: Vascular Endothelial Growth Factor (VEGF) Splice Isoforms May Hold The Key To Targeting Tumour Angiogenesis In Oesophageal Cancer
Biography
Biography: Farhan Mehedi
Abstract
Background & Aim: Angiogenesis is principally induced by vascular endothelial growth factor A (VEGF-A). However, the use of VEGF-A inhibitors in the treatment of esophageal cancer (e.g. Bevacizumab) has not proven efficacious in clinical trials. It has subsequently been shown that splicing of the terminal exon of VEGF-A pre-mRNA generates two separate isoforms: Pro-angiogenic VEGF165a and anti-angiogenic VEGF165b. These isoforms are balanced to regulate angiogenesis by the splicing factor SRSF1, phosphorylated by serine-arginine protein kinase1 (SRPK1). The aim of this study was to investigate expression of VEGF-A, its isoforms and SRPK1 in esophageal cancer and their association with micro vessel density (MVD) and patient survival. Understanding the role of SRPK1 and VEGF-A splice isoforms in the regulation of esophageal cancer angiogenesis may provide a new and potentially efficacious target for anti-angiogenic therapy.
Method: Tumor samples from 36 patients with esophageal adenocarcinoma undergoing curative resection following neo-adjuvant chemotherapy were examined using immunohistochemistry for VEGF-A, VEGF165a, VEGF165b, CD31 (for MVD) and SRPK1. Digital droplet PCR was used to quantify SRPK1 levels at the gene level.
Result: VEGF-A was not associated with MVD. There was a high (pro-angiogenic) VEGF165a/VEGF165b ratio in the majority of the esophageal cancers examined. VEGF165a expression was positively correlated with SRPK1 expression (p=0.01). There was a positive correlation between the pro-angiogenic (VEGF165a dominant) esophageal cancers, MVD and poor overall survival. However, this did not reach statistical significance.
Conclusion: The dominance of the pro-angiogenic VEGF splice isoform and the splicing factor SRPK1 show greater correlation with esophageal cancer angiogenesis and disease survival than the general target of VEGF-A. Further investigation of the control and potential inhibition of this angiogenic pathway in esophageal cancer is required.