Prognostic Value of Matrix Metalloproteinase 9 Expression inBreast Cancer Patients: A Meta-analysis

Background: Matrix metalloproteinase 9 (MMP-9) is related to tumor invasion and metastasis. However,the role of MMP-9 expression in breast cancer survival remains controversial. The purpose of this study wasto accomplish a more accurate estimation of the association between MMP-9 expression and survival results inbreast cancer patients through meta-analysis.
Methods: A meta-analysis of published studies investigating theeffects of positive MMP-9 expression on both relapse free survival (RFS) and overall survival (OS) was performed.Relevant literature was confirmed by searching electronic databases including PubMed, Ovid, EMBASE andChina National Knowledge Infrastructure (CNKI) before November 1, 2012. Individual hazard ratios (HRs)and 95% confidence intervals (CIs) were extracted and pooled HRs with 95% CIs were used to evaluate thestrength of the association between positive MMP-9 expression and survival results of breast cancer patients.Funnel plot and Egger’s regression tests were used to evaluate publication bias. Heterogeneity and sensitivityanalysis was also conducted. All the work was completed using STATA.
Results: A total of 2,344 patients from15 evaluative studies were finally included. Pooled HRs and 95% CIs suggested that MMP-9 overexpression hadan unfavorable impact on both OS (HR: 1.70, 95% CI: 1.41-2.04) and RFS (HR: 1.54, 95% CI: 1.17-2.01) inbreast cancer patients. There was no significant heterogeneity observed in the studies reported for OS (P=0.360,I2=8.8%), but not RFS (P=0.002, I2=67%). Publication bias was absent among the studies both in OS and RFScases (t=-0.54, P=0.605 and t=1.71, P=0.131, respectively). Omission of any single study had little effect on thecombined risk estimates on sensitivity analysis.
Conclusion: The results of this meta-analysis suggest that positiveMMP-9 expression confers a higher risk of relapse and a worse survival in patients with breast cancer. Largerprospective studies are now needed to evaluate the clinical utility of MMP-9 expression.