Fujimoto Daisuke, Hirono Yasuo, Goi Takanori, Katayama Kanji, Yamaguchi Akio
First Department of Surgery, Faculty of Medicine, University of Fukui, Fukui 910-1193, Japan.
Anticancer Res. 2008 Mar-Apr;28(2A):847-54.
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.
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.
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.
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.
蛋白酶激活受体（PARs）被认为参与了各类癌症的侵袭和转移过程。基质金属蛋白酶-1（MMP-1）在癌症侵袭和组织重塑中发挥作用。据报道，MMP-1可通过PAR-1改变癌细胞行为，促进细胞迁移和侵袭。我们探讨了PAR-1和MMP-1的表达与胃癌进展是否相关。
使用抗PAR-1和抗MMP-1小鼠单克隆抗体对129例胃癌样本进行免疫组织化学研究。对免疫染色与临床病理因素之间的关联进行统计学分析。
58例癌组织PAR-1表达呈阳性。PAR-1的表达与壁层浸润深度和腹膜播散有关。42例癌组织PAR-1和MMP-1表达均呈阳性，这与组织学分期、壁层浸润深度、淋巴结转移和腹膜播散有关。这些患者的预后明显比表达阴性肿瘤的患者差。多因素分析表明，PAR-1表达以及PAR-1和MMP-1联合表达是独立的预后因素。
这些结果使我们相信，PAR-1和MMP-1的表达与胃癌进展相关，是独立的预后预测指标。
