The VEGFR-2 protein and the VEGFR-2 rs1870377 A>T genetic polymorphism are prognostic factors for gastric cancer

ABSTRACT

Objective: Angiogenesis is one of the key processes in the development of malignant tumors. The vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) signaling pathway regulates branching angiogenesis in cancer. In this study, we analyzed the associations of VEGF/VEGFR-2 proteins and VEGFR-2 genetic variations with the prognosis of gastric cancer (GC).

Method: We collected the clinical information of patients with GC and extracted genomic DNA from paraffin-embedded tissues. Immunohistochemical methods were used to detect the expression of VEGF and VEGFR-2 in GC tissues. Four single nucleotide polymorphisms of VEGFR-2 were detected by the TaqMan assay. The Kaplan-Meier method and Cox regression model were applied to analyze the associations between clinicopathological characteristics, VEGFR-2 polymorphisms and GC prognosis.

Results: A total of 256 cases of GC were included in our study. VEGFR-2 (+) and VEGFR-2 (++/+++) protein expression levels were detected in 83 and 135 cases, respectively. High expression of the VEGFR-2 protein was associated with the poor prognosis of GC (log-rank test P = 0.026). No statistical significance was observed for the association between VEGF and the prognosis of GC. The VEGFR-2 rs1870377 A > T genetic polymorphism was discovered to be associated with the prognosis of GC (AA vs. AT, HR = 1.69, 95% CI = 1.06–2.68, P = 0.027).

Conclusion: Our study suggested that the high expression of VEGFR-2, as well as the VEGFR-2 rs1870377 A > T genetic polymorphism, may be prognostic markers for GC.

Keywords:

• VEGF/VEGFR-2
• gastric cancer
• prognosis
• VEGFR-2 genetic polymorphism

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Ethical Standards

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Additional information

Funding

This study was supported by funding from Shanghai Municipal Commission of Health and Family Planning, China (Grant No. 201540271), Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China (Grant No.15LC05 and No. 13YJ22), the Science and Technology Commission of Shanghai Municipality, China (Grant No.15ZR1427700).