title: Prognostic value of matrix metalloproteinase-1/ proteinase-activated receptor-1 signaling axis in hepatocellular carcinoma.
abstract: Matrix metalloproteinase-1 (MMP-1) is proposed to be involved in both tumor cell invasion and metastasis. MMP-1 proteolytically activates protease activated receptor-1 (PAR-1), which also plays an important role in tumor development and progression. However, it is currently unknown whether MMP-1 activation of PAR-1 has relevance to the progression of hepatocellular carcinoma (HCC). To address this problem, we investigate the clinicopathological and prognostic value of MMP-1/PAR-1 signaling axis in HCC. Immunohistochemistry assay was used to determine the expression of MMP-1 and PAR-1 proteins in normal and HCC tissues. The correlations of MMP-1 and PAR-1 expression with clinicopathological parameters were assessed by Chi-squared test. Patient survival and their differences were determined by Kaplan-Meier method and log-rank test. Cox regression was adopted for multivariate analysis of prognostic factors. MMP-1 and PAR-1 immunoreactivities were negative or low in normal liver tissues, but high in HCC tissues. PAR-1 expression was significantly correlated with that of MMP-1 (r = 0.896, p < 0.0001). The overexpression of MMP-1 and PAR-1 was significantly associated with recurrence, TNM staging and portal vein invasion of HCC. Patients with high MMP-1 and PAR-1 expression had significantly poorer overall survival (OS) (both P < 0.001) and disease-free survival (DFS) (both P < 0.001) when compared with patients with the low expression of MMP-1 and PAR-1. On multivariate analysis, MMP-1 and PAR-1 expression patterns were found to be independent prognostic factors for OS (both P < 0.001) and DFS (both P < 0.001). Our results suggest for the first time that the MMP-1/PAR-1 signaling axis might be applied as a novel marker for the prediction of recurrence and metastasis potency and a significant indicator of poor prognosis for patients with HCC.
authors: National Hepatobiliary & Enteric Surgery Research Center, Central South University, Changsha, Hunan, 410008, Peoples Republic of China.
authors: Mingmei
authors: M
authors: Liao
authors: Ping
authors: P
authors: Tong
authors: Jinfeng
authors: J
authors: Zhao
authors: Yangde
authors: Y
authors: Zhang
authors: Zhehai
authors: Z
authors: Li
authors: Jiwei
authors: J
authors: Wang
authors: Xueping
authors: X
authors: Feng
authors: Man
authors: M
authors: Hu
authors: Yifeng
authors: Y
authors: Pan
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D044463:Receptor, PAR-1 / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D044463:Receptor, PAR-1; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1