Clinicopathological and Prognostic Outcomes of VEGF Expression in Resected Gastric Cancer Tissues. A Systematic Review

Background: Vascular endothelial growth factor VEGF families have been implicated in prognosis and clinicopathological outcomes in patients with gastric cancer. This review aims to assess the relationship of clinicopathological and prognostic outcomes of patients with gastric cancer, present with overexpression of VEGF families in gastric cancer tissues. Methods: Full-published studies regarding clinicopathological and prognostic outcomes of patients with gastric cancer present with overexpression VEGF families sought through PubMed, MEDLINE, EMBASE and HINARI. The exclusion criteria for the reviewed literature were as follows. (1) The studies involved neoadjuvant or preoperative chemotherapy, chemoradiotherapy and target therapy. (2) Non-English articles. (3) The patients had multiple tumors. (4) The data sample was not reliable (5). The studies analyze the expression of VEGF in blood serum. STATA SE v. 13.1 (STATA_ Corporation, Texas, USA) has been used to analyze data. Statistical significant p-value was taken to be P<0.05 and two sided alpha of 5% implemented to determine confidence intervals and p-values. The outcomes of interest were clinicopathological and prognostic outcomes. Results: In this review, 96 studies identified and left twelve eligible literatures to assess the clinicopathological and prognostic outcomes of VEGF expression in patients with gastric cancer. VEGF-A expression was found to be significantly associated with the size of the tumor (P=0.028), increase the risk of positive lymph nodes (P=0.002) and lymphovascular invasion (P=0.001). Also, it was found to be associated with poor prognosis for overall survival and disease-free survival in patients with gastric cancer. Studies have shown patients with high expression of VEGF-C protein had significantly poorer prognoses than a group with low VEGF-C expression. Also, expression of VEGF-C was evaluated, and it showed a substantial relation to TNM staging, vascular, and lymphatic invasion (P<0.01). The expression of VEGF-D in gastric cancer tissue correlated significantly with the size of the tumor, invasion to lymphatic and venous tissues and distant metastasis, all these contribute to the TNM stage, and it is useful in the evaluation of prognosis of gastric cancer patients regarding progression-free survival and overall survival. Conclusion: This systematic review demonstrated that VEGF protein, especially VEGF-A, C and D overexpression in gastric cancer, all associated with poor prognosis and clinicopathological outcomes. We recommend that VEGF be a prognostic and predictive marker, and measured in all resected gastric cancer tissues to predict prognosis and clinicopathological outcomes of patients with gastric cancer.