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Background  Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Radiotherapy plus concomitant and adjuvant TMZ chemotherapy is the current standard of care for patients with GBM. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, are key modulators of tumor invasion and metastasis due to their ECM degradation capacity. The aim of the present study was to identify the most informative MMP member in terms of prognostic and predictive ability for patients with primary GBM.    Method  The mRNA expression profiles of all MMP genes were obtained from the Chinese Glioma Genome Atlas (CGGA), the Repository for Molecular Brain Neoplasia Data (REMBRANDT) and the GSE16011 dataset. MGMT methylation status was also examined by pyrosequencing. The correlation of  MMP9  expression with tumor progression was explored in glioma specimens of all grades. Kaplan–Meier analysis and Cox proportional hazards regression models were used to investigate the association of  MMP9  expression with survival and response to temozolomide.    Results   MMP9  was the only significant prognostic factor in three datasets for primary glioblastoma patients. Our results indicated that  MMP9  expression is correlated with glioma grade (p<0.0001). Additionally, low expression of M MP9  was correlated with better survival outcome (OS: p = 0.0012 and PFS: p = 0.0066), and MMP9 was an independent prognostic factor in primary GBM (OS: p = 0.027 and PFS: p = 0.032). Additionally, the GBM patients with low  MMP9  expression benefited from temozolomide (TMZ) chemotherapy regardless of the  MGMT  methylation status.    Conclusions  Patients with primary GBMs with low  MMP9  expression may have longer survival and may benefit from temozolomide chemotherapy.

plos one

Comparative Analysis of Matrix Metalloproteinase Family Members Reveals That MMP9 Predicts Survival and Response to Temozolomide in Patients with Primary Glioblastoma