Elevated Matrix Metalloproteinase-9 Expression Correlates With Advanced Stages of Oral Cancer and Is Linked to Poor Clinical Outcomes

Abstract

Using a meta-analytic approach, the relation between increased matrix metalloproteinase-9 (MMP-9) expression, tumor stage, and clinical outcomes in oral cancers was investigated. Multiple English- and Chinese-language electronic databases were searched to identify high-quality case-and-control studies relevant to this meta-analysis. Methodologic quality of the included trials was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology statement to ensure consistency in reviewing and reporting the results. Statistical analyses were carried out with STATA 12.0 statistical software. Nine case-and-control studies containing a combined total of 419 patients with oral cancer were included in the present meta-analysis. Results showed that patients who were positive for MMP-9 expression had a significantly poorer overall survival compared with those negative for MMP-9 (effect size= 2.10; 95% confidence interval, 0.98 to 3.22; P < .001). MMP-9 expression also positively correlated with lymph node metastasis and advanced T-stage groups (P < .05 for all comparisons). Further, high MMP-9 expression level correlated with increased oral cancer risk in Asians (P < .05 for all comparisons) as shown by method-stratified subgroup analysis. The present results strongly suggest that MMP-9 expression level influences tumor invasion and metastasis in oral cancers. Based on these results, MMP-9 can be an excellent therapeutic target in patients with oral cancer.