Association of epidermal growth factor genotype with angiogenesis in Egyptian hepatocellular carcinoma and cirrhotic patients

Helwa, Iman; Raouf, Haiam A.; Kholoussi, Naglaa; Esmaiel, Nora N.; Abdelkawy, Rania F. M.

doi:10.4103/mxe.mxe_2_21

Association of epidermal growth factor genotype with angiogenesis in Egyptian hepatocellular carcinoma and cirrhotic patients

Authors

Abstract

Background
Worldwide, hepatocellular carcinoma (HCC) is considered a common cancer ranking number six. It is considered number four in Egypt, and is strongly related to hepatitis B and C viruses. In liver cirrhosis, epidermal growth factor (EGF) gene polymorphism genotype is linked to developing HCC. Nevertheless “vascular endothelial growth factor” (VEGF) and “angiopoietin-2” (Ang-2) play a major role as well. Among angiogenic proteins; VEGF is effective and has an effective role in neovascularization. Facts suggest its role in tumor progression and hepatocarcinogenesis.
Objective
The objective of this study was to evaluate the relationship among human EGF genotype and HCC through monitoring of the potent angiogenic proteins (VEGF and Ang-2).
Methods
A total of 81 adults were prospectively enrolled and stratified into three groups: apparently healthy participants ( = 15), patients suffering from liver cirrhosis ( = 29), and HCC ( = 37). Genotyping of EGF single-nucleotide polymorphism was carried out in whole blood of the study participants by sequencing directly using ABI3730XL sequencer. In addition, serum VEGF and Ang-2 levels were determined in all participants using enzyme-linked immunosorbent assay technique.
Results
The study results revealed that six participants of the 61GA heterozygote genotype group (four cirrhosis and two HCC) had high VEGF levels compared with three participants of the 61GG wild-type homozygote group (one cirrhosis and two HCC) and nine participants of the 61AA homozygote genotype group (three controls, one cirrhosis, and five HCC). Moreover, Ang2 was 1.5-fold upregulated in four HCC patients with homozygote genotype compared with three participants of the heterozygote group (one cirrhosis and two HCC). Considerable upregulation was noted in VEGF levels in HCC and cirrhotic patients compared with controls. Also, Ang-2 levels increased in both the liver cirrhosis and HCC groups.
Conclusion
EGF polymorphism genotype (whether heterozygote or homozygote) is associated with increased levels of serum VEGF, an angiogenic protein related to risk for development of HCC. EGF genotype is related to risk for development of HCC in liver cirrhosis through its effect on VEGF and Ang-2 levels.

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