Collaborative overexpression of matrix metalloproteinase-1 and vascular endothelial growth factor-C predicts adverse prognosis in patients with gliomas

Abstract

Background and aim: Matrix metalloproteinase-1 (MMP-1), a member of the MMP family of zinc-dependent endopeptidases, has been detected to be strongly expressed in gliomas with high tumor grade and to be correlated with increased tumor invasiveness. Vascular endothelial growth factor-C (VEGF-C), which is able to induce MMP-1 transcription, has been found to be upregulated in glioblastoma compared to low grade gliomas and non-neoplastic brain. The aim of the present study was to investigate the clinical significance of the co-expression of MMP-1 and VEGF-C in glioma patients on determining the prognosis. Methods: One hundred and sixteen glioma patients (26 World Health Organization (WHO) grade I, 30 WHO grade II, 30 WHO grade III, and 30 WHO grade IV) and 15 non-neoplastic brain specimens acquired from 15 patients undergoing surgery for epilepsy as control were collected. Immunohistochemistry was used to evaluate the expression of MMP-1 and VEGF-C in glioma and non-neoplastic brain tissues. The correlations of collaborative MMP-1 and VEGF-C expression with selected clinicopathologic parameters and clinical outcome of glioma patients were also assessed. Results: Both MMP-1 and VEGF-C expression were significantly higher in glioma tissues compared to non-neoplastic brain tissues (both P<0.001). Of 116 glioma patients, 68 (58.62%) overexpressed MMP-1 and VEGF-C simultaneously. In addition, combined MMP-1 and VEGF-C expression was significantly associated with WHO grade (P<0.001) and Karnofsky performance status (KPS) score (P=0.01). Moreover, glioma patients expressing both MMP-1 and VEGF-C exhibited markedly poorer overall survival (P<0.001). According to the multivariate analyses, collaborative overexpression of MMP-1 and VEGF-C was found to be an independent prognostic factor for overall survival (P=0.009). Conclusions: Our data demonstrated for the first time that overexpression of both MMP-1 and VEGF-C may be an independent poor prognostic factor in gliomas, suggesting the interaction between MMP-1 and VEGF-C collaboratively stimulated advanced tumor progression and adverse outcome. Inhibiting both MMP-1 and VEGF-C could be a novel therapeutic approach for gliomas.