Influence of vascular endothelial growth factor single nucleotide polymorphisms on non-small cell lung cancer tumor angiogenesis

Maeda,Ai; Nakata,Masao; Yasuda,Koichiro; Yukawa,Takuro; Saisho,Shinsuke; Okita,Riki; Hirami,Yuji; Shimizu,Katsuhiko

doi:10.3892/or.2012.2075

Influence of vascular endothelial growth factor single nucleotide polymorphisms on non-small cell lung cancer tumor angiogenesis

Authors:
- Ai Maeda
- Masao Nakata
- Koichiro Yasuda
- Takuro Yukawa
- Shinsuke Saisho
- Riki Okita
- Yuji Hirami
- Katsuhiko Shimizu
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Affiliations: Department of General Thoracic Surgery, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
Published online on: October 9, 2012 https://doi.org/10.3892/or.2012.2075
Pages: 39-44
Copyright: © Maeda et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis. Several studies have reported that genomic VEGF polymorphisms may influence VEGF synthesis. To evaluate the role of VEGF single nucleotide polymorphisms (SNPs), we examined the expression of several angiogenesis-related proteins [VEGF, hypoxia-inducible factor-1α (HIF-1α) and delta-like ligand 4 (Dll4)] and the spread of microvessels in resected non-small cell lung cancer (NSCLC). Blood and tumor tissue from 83 patients with NSCLC were examined for VEGF -460T/C (rs833061) and VEGF +405G/C (rs2010963) SNPs using the SNaPshot method. Immunohistochemical staining was performed to measure protein expression and microvessel density (MVD). VEGF -460T/C and +405G/C SNPs showed no association with VEGF or HIF-1α expression and MVD. Patients with VEGF -460TT and the TC genotype had significantly higher MVD compared to those with the CC genotypes. Furthermore, patients with the VEGF -460TT genotype had significantly higher Dll4 expression compared to those with the TC or CC genotypes, while the VEGF +405G/C SNP displayed no association with Dll4 expression and MVD. These findings indicate that the VEGF -460T/C SNP may have a functional influence on tumor angiogenesis in NSCLC. We hypothesize that VEGF SNPs may influence angiogenesis through Dll4.

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