Prognostic value of protease-activated receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP-1) in gastric cancer

Background: Protease-activated receptors (PARs) are proposed to be involved in the invasive and metastatic processes of various types of cancer. Matrix metalloproteinase-1 (MMP-1) plays a role in cancer invasion and tissue remodelling. It has been reported that MMP-1 can alter the behavior of cancer cells through PAR-1 to promote cell migration and invasion. We considered whether the expression of PAR-1 and MMP-1 has relevance to progression in gastric cancer. Materials and Methods: An immunohistochemical study was carried out on 129 samples of gastric cancer using anti-PAR-1 and anti-MMP-1 mouse monoclonal antibodies. Associations between immunostaining and clinicopathological factors were analyzed statistically. Results: There were 58 carcinomas positive for PAR-1 expression. The expression of PAR-1 was associated with the depth of wall invasion and peritoneal dissemination. There were 42 carcinomas positive for both PAR-1 and MMP-1 expression which was associated with the histological stage, depth of wall invasion, lymph node metastasis and peritoneal dissemination. These patients had a significantly poorer prognosis than those with expression-negative tumors. Multivariate analysis indicated that PAR-1 expression and combined PAR-1 and MMP-1 expression were independent prognostic factors. Conclusion: The results led us to believe that the expression of PAR-1 and MMP-1 is associated with the progression of gastric cancer and an independent prognostic predictor.