| Objective:Vascular endothelial growth factor(VEGF)orvascular permeability factor(VPF)is a wide varieties of glycoproteins,distributed in the human brain,liver,spleen,lung,kidney and other organs widely.Vascular endothelial growth factor-D(VEGF-D)is one of several members of the VEGF family,and it is closely associated with angiogenesis and lymphangiogenesis.Up to now,there has been a lot of researches about VEGF-D involved in the development of gastric cancer in the domestic and overseas,but the results are not identical.By searching therelated literatures at home and abroad,we investigated the correlation between the immunohistochemical expression of VEGF-D and gastric cancer with the method of Meta analysis.Methods:PubMed,EMBASE,the Cochrane Library and China National Knowledge Infrastructure(CNKI)were searchedfor the literaturesabout the association of theimmunohistochemical expression of VEGF-D and gastric cancer.We also retrieved relevant literatures by manual retrieval.We extracted the relevant clinical parameters data between VEGF-D and gastric cancer.The odds ratio(OR),mean difference(MD)and 95%confidence interval(CI)of total effect were calculated byReview Manager 5.3(RevMan 5.3)statistical software.And then we could make dichotomous and continuous Meta analysis.Results:First,234 articles were screened out through searching the database and manual searching.According to the inclusion and exclusion criteria,the final total sample size of gastric cancer was 2666 cases.1830 males,836 females,average age: 23-90 years old(mean age: 58.7 years old).The results showed that the expression rate of VEGF-D was higher in gastric cancer tissues than non gastric cancer tissues(OR=9.00,95%CI=[6.66,12.18],P<0.00001),but significant heterogeneity was found among the studies(P=0.05,I2=36%).Subgroup analysis showed that the immunohistochemical staining method(P=0.01)could partially explain the source of heterogeneity.There was no significant difference between the level of VEGF-D expression in undifferentiated and differentiated gastric cancer(OR=1.70,95%CI=[1.01,2.86],P=0.05).And there also had a high degree of heterogeneity(P<0.00001,I 2 =78%).We found that the source of antibody(P=0.01),the evaluation method of result(P< 0.00001)are both of the source of heterogeneity by subgroup analysis.Although the expression rate of VEGF-D in serosa invasion group was higher than negative control group with significant difference(OR=2.05,95%CI=[1.46,2.87],P<0.0001),but we also found heterogeneity(P=0.02,I2=48%).By the analysis of subgroup,the evaluation method of result(P=0.04)can partially explain the source of heterogeneity.In VEGF-D(+)group,lymph vessel density(LVD)was greater than VEGF-D(-)group(MD=5.38,95%CI=[3.11,7.66],P<0.00001)with obvious heterogeneity(P<0.00001;I2=96%).The antibody type of VEGF-D(0.008)and the method of immunohistochemical staining(P=0.0006)were contributing to partial heterogeneity.The expression rate of VEGF-D in lymphatic invasion(+)group,vascular invasion(+)group,lymph node metastasis(+)group and TNM III-IV group were significantly higher than those in their negative control groups(OR=2.72,95%CI=[1.96,3.78],P<0.00001;OR=1.87,95%CI=[1.24,2.82],OR=3.42,95%CI=[2.81,P=0.003;4.16] P< 0.00001;OR=0.25,95%CI=[0.19,0.33],P< 0.00001),and there were no significant heterogeneity(P=0.41,I2=3%;P=0.84,I2=0%;P=0.18,I2=20%;P=0.42,I2=3%).Conclusion:The immunohistochemical expression of VEGF-D had an obvious relevance with gastric cancer tissues,the depth of invasion,LVD,the vascular invasion,the lymphatic invasion,the lymph node metastasis,the TNM stage of gastric cancer.There was no association between VEGF-D and the histological grade of gastric cancer.It might help uschoose the treatment planning and evaluate the prognosis of gastric cancer. |
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