Upregulation of matrix metalloproteinase-1 and proteinase-activated receptor-1 promotes the progression of human gliomas

Abstract

Objective To investigate the effect of matrix metalloproteinase-1 (MMP-1) and proteinase-activated receptor-1 (PAR1) on the progression of human gliomas.Methods Immunohistochemical staining was performed to detect the expression patterns of MMP-1 and PAR1 in biopsies from 108 patients with primary gliomas.Kaplan-Meier survival and Cox regression analyses were done to evaluate the prognosis of patients.Results Immunostaining revealed MMP-1 to be expressed in 83.3％ (90/108) and PAR1 in 76.9％ (83/108) of the biopsies respextively.PAR1 expression was significantly correlated with that of MMP-1 (r =0.8,P ＜ 0.01 ).The total immunohistochemistry (IHC) scores for MMP-1 and PAR1 were significantly higher in high-grade tumors than in low-grade tumors (both P ＜ 0.01 ).In addition,patients with high MMP-1 and high PAR1 expression had lower Kamofsky performance scale (KPS) scores than those with low MMP-1 and low PAR1 expression (both P ＜0.01 ).Moreover,MMP-1 and PAR1 expression was shown to be a strong prognostic marker for decreased overall survival (P ＜ 0.01,respectively).Furthermore,Cox multi-factor analysis showed that KPS ( P ＜ 0.01 ),WHO grade ( P ＜ 0.01 ),MMP-1 ( P ＜ 0.01 ),and PAR1 (P ＜ 0.01 ) were independent prognostic factors for human gliomas.Conclusion Our results suggest that in gliomas,the upregulation of MMP-1 and PAR1 correlates with histological malignancy grade and clinical outcome. Key words: Gliomas; Matrix metalloproteinase; Proteinase-activated receptor; Prognosis