combined upregulation of matrix metalloproteinase-1 and proteinase-activated receptor-1 predicts unfavorable prognosis in human nasopharyngeal carcinoma

Rui Yang,1 Yu Xu,2 Peizhong Li,2 Xin Zhang,2 Junying Wang,2 Dongsheng Gu,2 Yao Wang31State 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; 2Department of Otorhinolaryngology, Huai'an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China; 3Pharmaceutical Preparation Section, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, People’s Republic of ChinaBackground: 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. Conclusion: 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.Keywords: MMP-1, PAR-1, nasopharyngeal carcinoma, coexpression, prognosis