| Objective:The role of vascular endothelial growth factor C(VEGFC)expression in colorectal cancer progression and prognosis has been studied for many years,but the results remain controversial.We systematically evaluated the evidence of VEGFC expression in colorectal cancer to shed light on this issue.Methods:Databases such as Web of Science,PubMed,EMBASE,Cochrane Library,CNKI,Chinese Biomedical Literature,VIP and Wanfang were searched to determine the association between VEGFC overexpression and overall survival(OS),disease-free survival(DFS)and clinicopathological characteristics of colorectal cancer patients.HR was combined with 95% CI to evaluate the association between VEGFC expression levels and OS and DFS in colorectal cancer patients.OR was combined with 95% CI to evaluate the association between the expression level of VEGFC and clinicopathological parameters.The c Bio-Portal database was used to screen the co-expressed genes of VEGFC in colorectum;followed by gene ontology GO and KEGG enrichment analysis in DAVID database;the PPI network interacting with VEGFC was constructed using STRING database;the GEPIA database was used to verify the relationship between VEGFC expression and prognosis of colorectal cancer and the PPI network was used to Finally,the correlation between VEGFC expression in colorectal cancer and the level of immune cell infiltration was done using TIMER database.Results:A total of 7956 studies were retrieved for this meta-analysis,and the final 94 studies with 7797 colorectal cancer patients were included for analysis.The results showed a significant(P<0.00001)association between high VEGFC expression and poorer OS(HR=2.29,95% CI = 1.90-2.76)and DFS(HR =2.53,95% CI=1.80-3.57).In addition,the results showed that high VEGFC expression was associated with tumor stage(TNM stage(OR = 0.42;95% CI = 0.33-0.53)and Ducks stage(OR =3.49;95% CI = 2.80-4.88)),T stage(OR = 2.32;95% CI = 2.00-2.71),tumor diameter(OR = 0.77.95% CI = 0.58-1.02),lymph node metastasis(OR = 4.75;95% CI =4.05-5.58),distant metastasis(OR = 2.50;95% CI = 1.66-3.76),venous invasion(OR= 1.96;95% CI = 1.36-2.83),and lymphatic invasion(OR = 3.90;95% CI =2.79-5.47),degree of differentiation(OR = 0.69;95% CI = 0.55-0.88)and differences in VEGFC expression in colorectal or paracancerous tissues(OR = 0.13;95% CI =0.10-0.16)were significantly(P<0.01)associated;and with gender(OR = 1.03;95%CI = 1.90-2.76;P = 0.61),age(median age at 60 years(OR = 0.99;95% CI =0.83-1.19;P = 0.94);median age at 50 years(OR = 0.82;95% CI = 0.59-1.14;P =0.25)and tumor location(OR = 1.06;95% CI = 0.77-1.44;P = 0.73)all showed no significant correlation.Enrichment analysis revealed a role for VEGFC and its co-expressed genes in promoting cell proliferation,inhibiting apoptosis and promoting intercellular adhesion;in addition,VEGFC was significantly correlated with PIK3 CA,GRB2,SHC1,NTRK1,KDR,ITGB1,FLT1,FLT4,ITGA9,NRP2 in colorectal cancer;and with immune cell infiltration A significant association was observed between.Conclusions:1)High VEGFC expression leads to progression and poor prognosis in colorectal cancer.2)VEGFC is likely to be a prognostic biomarker and therapeutic target for patients with colorectal cancer. |
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