Relationship Between Expression And Polymorphism Of MMPs Gene And Esophageal Cancer: A Meta Analysis

OBJECTIVE: In order to elucidate the relationship between the expression and polymorphism of matrix metalloproteinases(MMPs)genes and esophageal cancer,various studies have been conducted by domestic and foreign scholars,but the results are still controversial.In this study meta-analysis was used to further determine the relationship between changes in MMPs gene expression and clinical characteristics of esophageal cancer,as well as between gene polymorphism and esophageal cancer susceptibility.METHODS:The Chinese and English databases were searched by computer to collect relevant literatures from the database construction to March 2019.The literatures were screened according to the inclusion criteria,and the quality of the included literatures was evaluated by NOS scale.Relevant subjects and data were extracted from the included literatures according to the research needs.The forest map was drawn with StataMP 14 software,and the data was analyzed statistically.Funnel plot was drawn for publication bias analysis.The odds ratio(OR)and its 95%confidence interval(95%CI)were selected as statistical indicators to combine the effect size.Q test was used to test the heterogeneity between studies.Z test was used to test the significance of the differences between groups.According to the heterogeneity selection effect model,subgroup analysis and sensitivity analysis were carried out for the studies with heterogeneity.RESULTS: In the meta-analysis of the relationship between the expression of MMPs and the clinical features of esophageal cancer,a total of 77 literatures and 90 studies were included,including 4901 cases of esophageal cancer tissues and 2215 cases of non-cancer control tissues.In the systematic evaluation of the included studies,we found that the overall positive expression of MMPs : the cases of esophageal cancer group was higher than the control group,TNM staging ?-?group was higher than ?-? group;The infiltration depth of T3-T4 group was higher than that of T1-T2 group,and the groups with lymph node metastasis were higher than those without lymph node metastasis.Meta-analysis of the case-controlstudies of the four types of MMPs showed that the expression of MMPs in esophageal cancer tissues was significantly higher than that of the control group.No factors affecting heterogeneity were found in the subgroup analysis,and sensitivity analysis and publication bias analysis further confirmed the stability of the results.Meta-analysis of the relationship between MMPs expression and clinical features showed that MMP-1 expression was significantly associated with TNM staging of esophageal cancer(OR=0.497,95% CI: 0.359-0.688);MMP-2 expression was significantly correlated with TNM staging(OR=0.340,95% CI:0.214-0.542),invasion depth(OR=0.376,95% CI:0.189-0.746),lymph node metastasis(OR=2.126,95% CI:1.247-3.625)and differentiation degree(OR=1.386,95% CI:1.044-1.839)of esophageal cancer.MMP-7 expression was significantly correlated with TNM staging(OR=0.230,95% CI:0.145-0.365),invasion depth(OR=0.405,95%CI:0.236-0.695)and lymph node metastasis(OR=2.358,95% CI:1.603-3.470)of esophageal cancer.MMP-9 expression was significantly correlated with TNM staging(OR=0.302,95% CI:0.150-0.608),invasion depth(OR=0.284,95%CI:0.163-0.494),lymph node metastasis(OR=3.023,95% CI:2.031-4.500)and differentiation degree(OR=0.528,95% CI:0.354-0.789)of esophageal cancer.In the Meta analysis of the relationship between MMPs gene polymorphism and esophageal cancer susceptibility,a total of 14 literatures were included.20 studies included 3296 patients with esophageal cancer and 4464 controls.The main results of the meta-analysis showed that: MMP-2 1306 C/T and MMP-9 279 R/Q gene polymorphisms were significantly correlated with the susceptibility of esophageal cancer,and the occurrence of gene polymorphisms may reduce the risk of esophageal cancer.The significant differences of MMP-2 1306 C/T were mainly found in the model of alleles(C vs T:OR=1.313,95% CI: 1.137-1.518),dominant genes(CC vs(CT+TT): OR=1.361,95% CI: 1.156-1.601),superdominant genes((CC+TT)vs CT:OR=1.329,95% CI: 1.124-1.570)and codominant genes(CC vs CT: OR=13.643,95% CI: 4.939-37.281).The significant differences of MMP-9 279 R/Q were mainly found in the model of recessive genes(R vs Q: OR=1.251,95% CI: 1.020-1.534),codominant genes(RR vs(QQ+RQ): OR=4.545),95% CI: 1.243-16.621)and superdominant genes(RR vs RQ: OR = 4.545,95% CI: 1.243-16.621).MMP-7 181A/G and MMP-9 1562 C/T gene polymorphisms were significantly associated with esophageal cancer susceptibility,and the presence of genetic polymorphisms may increase the risk of esophageal cancer.The significant differences of MMP-7 181A/G were mainly found in the model of allele(A vs G: OR=0.566,95% CI:0.425-0.753),dominant gene(AA vs(AG+GG): OR=0.495,95% CI: 0.344-0.712),superdominant gene(AG vs(AA+GG): OR=0.591,95% CI: 0.410-0.853)and codominant gene(AA vs GG: OR=0.439,95% CI: 0.237-0.813).The significant differences of MMP-9 1562 C/T were mainly found in the model of allele(C vs T:OR=0.755,95% CI: 0.612-0.931),recessive gene((CC+CT)vs TT: OR=0.451,95%CI: 0.250-0.811)and codominant gene(CT vs TT: OR=0.439,95% CI: 0.243-0.795).The relationship between MMP-1 1607 1G/2G,MMP-2 735 C/T gene polymorphism and esophageal cancer susceptibility still needs further study.CONCLUSION:MMP-1,MMP-2,MMP-7 and MMP-9 are overexpressed in esophageal cancer and correlated with clinicopathological characteristics,which can be used as an indicator for early diagnosis and prognosis of esophageal cancer.MMP-2 1306 C/T,MMP-7-181a/G,MMP-9 279 R/Q and MMP-9 1562 C/T gene polymorphisms were significantly correlated with esophageal cancer susceptibility,which have certain application value for the early screening of the susceptible population of esophageal cancer,but they still need to be confirmed by further studies.