Association Of VEGFR-3 Expression With Clinicopathological Features And Prognosis In Gastric Cancer:A Meta-analysis

Objective:To investigate the association of VEGFR-3 expression with clinicopathological features and prognosis in gastric cancer.Methods:Retrieved English and Chinese databases such as Pub Med、Ovid、Cochrane Library、CNKI、Wanfang Data、VIP and so on from their inception to December 2015,supplemented by manual retrieval and literature backtracking,to collect casecontrol studies about the association of VEGFR-3 expression with clinicopathological features and prognosis in gastric cancer.According to the inclusion and exclusion criteria,two researchers respectively preliminary screened literatures,and then used the NOS case-control study quality assessment scale to evaluate the quality of literatures,finally adopted high quality literatures and extracted relevant data.Metaanalysis was conducted using the software of Rev Man 5.3.The evaluation indicators included age,gender,tumor size,differentiation,invasion depth,lymph node metastasis,vessel invasion,TNM staging and five-year survival rate.The existence of publication bias was evaluated by funnel plot and egger test.Results:A total of 11 case-control studies comprising 994 samples is included. All the studies use immunohistochemical method to determine the expression of VEGFR-3.The meta-analysis results show that the expression of VEGFR-3 is associate with invasion depth,lymph node metastasis and five-year survival rate(P<0.05),although it isn’t related to age,gender,tumor size,differentiation,vessel invasion and TNM staging(P>0.05).The probability of T3-4 invasion is significantly higher in VEGFR-3 positive gastric cancer.This suggests that VEGFR-3 positive gastric cancer cells have a stronger ability of local invasion(OR=1.67,95%CI[1.19,2.34],P=0.003).Regional lymph node metastasis is more likely to occur in VEGFR-3 positive gastric cancer.VEGFR-3 can promote the growth of lymphatic vessels,enhance the ability of tumor cells to migrate through lymphatic vessels(OR=3.14,95%CI[1.67,5.88],P=0.0004).The five-year survival rate is significantly lower in VEGFR-3 positive gastric cancer patients.This suggests that the expression of VEGFR-3 is a poor prognostic factor of gastric cancer(OR=0.47,95%CI [0.32,0.71],P=0.0003).Conclusion:The expression of VEGFR-3 in gastric cancer was closely related to invasion depth,lymph node metastasis and five-year survival rate.VEGFR-3 can enhance the ability of local invasion and lymphatic migration of gastric cancer cells.Besides,it can promote the growth of lymphatic vessels in gastric cancer tissues.VEGFR-3 is an independent prognosis predictor of gastric cancer,it is negatively correlated with the five-year survival rate of patients with gastric cancer.Anti-VEGFR-3 targeted therapy may provide a new thought for the treatment of advanced gastric cancer with VEGFR-3 positive.