title: Collaborative overexpression of matrix metalloproteinase-1 and vascular endothelial growth factor-C predicts adverse prognosis in patients with gliomas.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Medical College, Shantou University, Shantou City, Guangdong Province 515041, China. xuym777@163.com
authors.forename: Yimin
authors.initials: Y
authors.lastname: Xu
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhong
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
authors.forename: Ziheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Quantang
authors.initials: Q
authors.lastname: Wei
authors.forename: Weizheng
authors.initials: W
authors.lastname: Song
authors.forename: Hongwu
authors.initials: H
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001932:Brain Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002648:Child; D005260:Female; D005910:Glioma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D008875:Middle Aged; D011379:Prognosis; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C; D020781:Matrix Metalloproteinase 1
keywords: Glioma; Immunochemistry; Matrix metalloproteinase-1; Prognosis; Vascular endothelial growth factor-C