The prognostic significance of vascular endothelial growth factor-D expression in colorectal cancer: a meta-analysis

Background: Vascular endothelial growth factor-D (VEGF-D) is a glycoprotein closely associated with lymphangiogenesis and angiogenesis. Although much research has been done on the relationship between VEGF-D and colorectal cancer, there is no agreed upon conclusion at present. We tried to summarize the reliable evidence on the use of the VEGF-D protein to estimate the prognostic and clinicopathological role of VEGF-D overexpression in colorectal cancer. Methods: Searching was performed in electronic databases to collect data without any language limits for original articles up through March 30, 2018. Furthermore, a meta-analysis was undertaken to evaluate the relationship between VEGF-D overexpression and the prognosis of patients with colorectal cancer, including disease-free survival (DFS), overall survival (OS), and clinicopathological characteristics. Results: 10 studies were included in the final analysis. 6 studies (n=730 patients) assessed the association between OS and VEGF-D overexpression. Statistics were calculated for OS (HR=0.91; 95% CI=0.33-1.49; P=0.002). Meanwhile, 3 studies (n=404 patients) evaluated the relationship between DFS and VEGF-D overexpression. Statistics were calculated for DFS (HR=1.28; 95% CI=0.95-1.60; P<0.001). When the studies were layered by the clinicopathological characteristics, including tumor stage (n=603; OR=2.19; 95% CI=1.54-3.12; P<0.001), T stage (n=263; OR=2.52; 95% CI=1.344.73; P=0.004); lymph node metastasis (n=655; OR=4.04; 95% CI=2.83-5.75; P<0.001), liver metastasis (n=298; OR=2.99; 95% CI=1.61-5.53; P=0.001), venous involvement (n=354; OR=0.93; 95% CI=0.60-1.45; P=0.758), lymphatic involvement (n=354; OR=1.38; 95% CI=0.81-2.36; P=0.242), and differentiation degree (n=655; OR=0.88; 95% CI=0.58-1.34; P=0.559), they provided important, objective, and extensive prognostic information. Conclusion: This study indicates that patients with VEGF-D overexpression have a shorter OS and DFS, higher levels of tumor stage and T stage, and easier lymph node and liver metastasis.