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

Cancer Biol Ther. 2019;20(4):497-504. doi: 10.1080/15384047.2018.1537575. Epub 2018 Oct 31.

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; VEGFR-2 genetic polymorphism; gastric cancer; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / surgery
  • Survival Rate
  • Vascular Endothelial Growth Factor Receptor-2 / genetics*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*

Substances

  • Biomarkers, Tumor
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2

Grants and 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).