a Department of Oncology, Xinhua Hospital, School of Medicine , Shanghai Jiao Tong University , Shanghai , China.
b Department of Pathology, Xinhua Hospital, School of Medicine , Shanghai Jiao Tong University , Shanghai , China.
Cancer Biol Ther. 2019;20(4):497-504. doi: 10.1080/15384047.2018.1537575. Epub 2018 Oct 31.
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).
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.
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).
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.
血管生成是恶性肿瘤发展的关键过程之一。血管内皮生长因子 (VEGF) 和 VEGF 受体-2 (VEGFR-2) 信号通路调节癌症中的分支血管生成。本研究分析了 VEGF/VEGFR-2 蛋白与 VEGFR-2 遗传变异与胃癌 (GC) 预后的关系。
我们收集了 GC 患者的临床信息，并从石蜡包埋组织中提取基因组 DNA。采用免疫组织化学方法检测 GC 组织中 VEGF 和 VEGFR-2 的表达。采用 TaqMan 法检测 VEGFR-2 的 4 个单核苷酸多态性。采用 Kaplan-Meier 法和 Cox 回归模型分析临床病理特征、VEGFR-2 多态性与 GC 预后的关系。
本研究共纳入 256 例 GC 患者。VEGFR-2 (+) 和 VEGFR-2 (++/+++) 蛋白表达水平分别在 83 例和 135 例中检测到。VEGFR-2 蛋白高表达与 GC 预后不良相关（对数秩检验 P=0.026）。VEGF 与 GC 预后无统计学意义。VEGFR-2 rs1870377 A>G 遗传多态性与 GC 预后相关（AA 与 AT，HR=1.69，95%CI=1.06-2.68，P=0.027）。
本研究表明，VEGFR-2 高表达以及 VEGFR-2 rs1870377 A>G 遗传多态性可能是 GC 的预后标志物。
