title: Combined upregulation of matrix metalloproteinase-1 and proteinase-activated receptor-1 predicts unfavorable prognosis in human nasopharyngeal carcinoma.
abstract: BACKGROUND
  The upregulation of matrix metalloproteinase-1 (MMP-1) has been demonstrated to be correlated with lymph node metastasis of nasopharyngeal carcinoma (NPC), while the activation of protease-activated receptor-1 (PAR-1) mediates proliferation and invasion of NPC cells. The present study investigated the clinical significance of the coexpression of MMP-1 and PAR-1 in NPC patients in determining the prognosis.
  
  
  METHODS
  Immunohistochemistry was performed to detect the expression of MMP-1 and PAR-1 in tumor tissue samples from 266 NPC patients.
  
  
  RESULTS
  Overexpression of MMP-1 and PAR-1 proteins were, respectively, detected in 190 (71.43%) and 182 (68.42%) of the 266 NPC patients. In addition, the combined MMP-1 and PAR-1 expression was significantly associated with advanced T-stage (P = 0.01), advanced clinical stage (P = 0.002), positive recurrence (P = 0.01), and metastatic status (P = 0.01) of NPC. Moreover, the overall survival in NPC patients with MMP-1 and PAR-1 dual overexpression was significantly shorter than in those with dual low expression (P < 0.001). Furthermore, the multivariate analyses indicated that the combined MMP-1 and PAR-1 overexpression was an independent prognostic factor for overall survival (P = 0.001) in NPC patients, but the upregulation of MMP-1 and PAR-1 alone was, in each case, not an independent prognostic factor for this disease.
  
  
  CONCLUSIONS
  Our data provide convincing evidence, for the first time, that the activation of the MMP-1 and PAR-1 axis may be involved in the tumorigenesis and progression of NPC. The upregulation of MMP-1 in combination with PAR-1 overexpression is an unfavorable prognostic marker for NPC and might offer the possibility of future therapeutic targets.
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center and Department of Cell Biology, Department of Clinical Nursing, School of Nursing, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Xu
authors.forename: Peizhong
authors.initials: P
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Junying
authors.initials: J
authors.lastname: Wang
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Gu
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
keywords: MMP-1; PAR-1; coexpression; nasopharyngeal carcinoma; prognosis