Overexpression of MMPs Functions as a Prognostic Biomarker for Oral Cancer Patients: A Systematic Review and Meta-analysis

Purpose: Matrix metalloproteinases (MMPs) are closely associated with the progression of oral cancer. This study is a meta-analysis of the published literature on MMPs and oral cancer prognosis. Materials and Methods: A comprehensive search of the literature on the prognosis of MMPs and oral cancer in PubMed, Embase, Web of science databases and the Cochrane Library was performed. All eligible studies were included in the final study and HR data were extracted. Pooled hazard ratio (HR) was analysed. Results: A total of 15 studies concerning 1266 patients were included for the meta-analysis. Pooled HR showed that overexpression of MMPs negatively influenced overall survival (OS) (HR = 2.18; 95% CI: 1.80-2.65; heterogeneity test, p = 0.080; I2 = 35.5%). In the subgroup analysis, the HR of MMP-2 was positive and the OS was poor (HR = 3.93; 95% CI: 2.19-7.07; weight 10.94%; heterogeneity test, p = 0.481; I2 = 0.0%). The HR of MMP-9 was positive and the OS was poor (HR = 1.96; 95% CI: 1.55-2.48; weight 68.12%; heterogeneity test, p = 0.115; I2 = 15.3%). A few articles showed that MMP-11 and -13 overexpression is associated with differences in OS. The combined HR showed that the overexpression of MMPs negatively afftected the disease-free time (DFS) (HR = 2.45; 95% CI: 1.49-4.05; heterogeneity test, p = 0.061; I2 = 50.2%). Overexpression of MMPs tends to worsen DFS. No publication bias was found in the current meta-analysis. Conclusion: MMP-9 and -2 overexpression was associated with poor prognostes in oral cancer patients. Therefore, early and accurate detection of MMP-9 and -2 levels can help improve the prognosis of MMP-9- and MMP-2-positive oral cancer patients. Keywords: meta-analysis, MMP family members, oral cancer, prognosis