Expression of MMP-14 and prognosis in digestive system carcinoma: a meta-analysis and databases validation

Background: The Matrix metalloproteinase-14 (MMP-14) expression has been shown to be overexpressed in different cancers. However, there is no comprehensive quantitative evaluation of the MMP-14 prognostic value in digestive system carcinoma (DSC). The aim of this study is to explore the correlation between the MMP-14 expression and DSC prognosis. Methods: We conducted a meta-analysis to estimate the association strength between MMP-14 expression and prognosis. GEPIA and Kaplan Meier plotters were used to assess overall survival (OS), disease-free survival (DFS)/progression-free survival (PFS) in DSC patients and the differential expression of MMP-14 in DSC tissues and adjacent tissues. Results: A total of 20 studies including 2,519 patients with OS and 438 patients with DFS/PFS data were analyzed in evidence synthesis. Overall, the combined hazard ratio (HR) with 95% confidence interval (95% CI) was 1.98 (95%Cl: 1.77-2.22, P<0.001) for OS and 3.61 (95%Cl: 2.39-5.43, P<0.001) for DFS/PFS. For subgroup analyses, significant correlations were revealed between increased MMP-14 expression and poor OS in patients with gastric cancer (HR=2.21, 95%CI: 1.76-2.77, P<0.001), esophageal carcinoma (HR=2.01, 95%CI: 1.58-2.57, P<0.001), oral cancer (HR = 1.69, 95% CI: 1.30-2.20, P < 0.001) (HR=2.14, 95%CI 1.35-2.19, P<0.001) and hepatocarcinoma. In database verification analyses, the MMP-14 expression levels in normal tissues were significantly higher than that in DSC tissues, and significant associations were observed between high MMP-14 expression levels and poor prognosis. Conclusions: The high expression levels of MMP-14 might predict poor prognosis in DSC. Larger prospective clinical cohort studies are required to validate the prognostic role.