VEGF gene sequence variation defines VEGF gene expression status and angiogenic activity in non-small cell lung cancer

Abstract

Different vascular endothelial growth factor (VEGF) gene polymorphisms have been shown to result in different VEGF gene responsiveness to various stimuli and different capacity for VEGF protein production. In the present study, we examined four VEGF gene polymorphisms in thirty–six individuals with non-small cell lung cancer (NSCLC). Gene polymorphisms were correlated with the VEGF protein expression in cancer cells and the tumor angiogenic activity. The −2578C/C, −634G/G and −1154A/A and G/A alleles in the VEGF gene were linked with low VEGF expression, while the −2578C/A, the −634 G/C and the −1154G/G alleles were linked with high VEGF expression. Tumors with −2578C/C had a significantly lower vascular density (VD) compared to the −2578C C/A. Similarly, cases with the −634G/G VEGF polymorphism had a singinificanltly lower vascular density compared to the combined C/C and G/C groups. In addition, the −1154A/A polymorphism seemed to relate with poor vaccularization but the difference did not reach significance. It is concluded that inherited VEGF sequence variations, which characterize the tumor genome itself, are strong determinants of the molecular VEGF and VEGF-downstream phenotype of NSCLC. The large variation in angiogenicity between tumors of similar histologic morphology emerges as a consequence of the ‘parental’ VEGF gene ability to produce VEGF.