Association Between Tissue Inhibitor of Metalloproteinase-3 Gene Methylation and Gastric Cancer Risk: A Meta-Analysis.

Abstract

The tumor suppressor gene tissue inhibitor of metalloproteinase-3 (TIMP-3) has been reported to be frequently and significantly downregulated in gastric cancer, and its downregulation is correlated with hypermethylation in its promoter region. However, the association between TIMP-3 methylation and gastric cancer risk remains unclear. In this study, we assessed the relationship between TIMP-3 promoter methylation and gastric cancer risk by performance of a meta-analysis. Relevant studies were identified in a comprehensive literature search using PubMed, Embase, and Web of Science databases. The strength of the association between TIMP-3 methylation and the risk of gastric cancer was assessed by odds ratio (OR) with the corresponding 95% confidence interval (CI). The heterogeneity among studies was tested using the Q-statistics and I(2) metric. The publication bias was examined by Begg's funnel plots and Egger's linear regression test. A total of 1096 subjects from eight studies were included in the present meta-analysis. Overall, a significant association between TIMP-3 methylation and gastric cancer risk was observed (OR = 8.65; 95% CI 4.31-17.37; p < 0.001). Stratified analyses by ethnicity, sample materials, and detection methods also revealed increased gastric cancer risk in individuals harboring methylated TIMP-3. Moreover, no publication bias was detected in the present meta-analysis. Our results show a positive correlation between TIMP-3 promoter methylation and gastric cancer risk and indicated that TIMP-3 promoter methylation may be used as a molecular marker for gastric cancer.