Expression Of ASK1 And MMP-9 In Gastric Cancer And Relationship With The Clinical Data

Background and Objective:Gastric cancer is a highly aggressive malignant tumor, which has a characteristics of late clinical presentation, advanced stage and extremely poor prognosis. The curative treatment for pancreatic cancer is surgery. Postoperative patients often accompany with recurrence and metastasis of tumor. Apoptosis signal-regulating kinase 1 (ASK1) acts upstream of JNK and p38 kinases. It phosphorylates and activates MKK4/MKK7 and MKK3/MKK6, which in turn induce JNK and p38 kinase activities, respectively. ASK1 plays a pivotal role in cell death induced by a variety of stimuli such as TNFa, H2O2 and anti-cancer drugs. The MMPs are a major group of enzymes which can degrade nearly all components of the extracellular matrix (ECM), as well as components of basement membranes. An elevated expression of MMPs contributes to various pathologic processes, including rheumatoid arthritis, osteoarthritis, angiogenesis, invasion, and metastasis in carcinoma. Two members of the MMP family, MMP-2 and MMP-9, are highly expressed in various tumors, including breast and bladder cancer. Serum levels of MMP-9, but not MMP-2, are significantly higher in colorectal and gastric cancer compared to controls. Elevated plasma MMP-9 correlates significantly with lymph node metastasis, lymphatic invasion, venous invasion, and had poorer survival rates.In the present study, we searched the exression of ASK1 and MMP-9 and their clinical significance in gastric cancer.Methods:Expression of ASK1 and MMP-9 in 53 gastric cancer group,29 normal gastric groups were detected by Ultrasensitive Streptavidin-Peroxidase immunohistochemistry staining.Results:The positive expression rate of MMP-9 in gastric cancer group and normal gastric group was 39.6% and 10.3% respectively. The expression rate of MMP-9 was higher in gastric cancer group than that of normal gastric group (P=0.005). The relationship between expression rate of MMP-9 and lymph node metastasis, depth of invasion, TNM stages and distant metastasis was significant(P<0.05). However, these was nosignificant correlation between expression of MMP-9 in gastric cancer and tumor size, sex, age, differential degree, tumor location, tumor diameter and Borrmann's type (P>0.05). These was a significant relationship in the positive expression rate of ASK1 between gastric cancer group and normal gastric group(59.5% vs 82.8%, P<0.05). The expression rate of ASK1 was higher in distant metastasis group than that of nondistant metastasis group in gastric cancer (P<0.05). But, there was no significant correlation between expression of ASK1 in gastric cancer and the tumor size, sex, age, tumor location, differential degree, Borrmann's type, depth of invasion, lymph node metastasis and TNM stages. (P<0.05). There was a positive correlation between the expression of ASKl and MMP-9, proved by the correlation test (rs=-0.570, P=0.000).Conclusion:1 The expression of MMP-9 was up-regulated in gastric cancer. These was a significant relationship between expression of MMP-9 and lymph node metastasis, depth of invasion, TNM stages and distant metastasis in gastric cancer.2 The expression of ASK1 was down-regulated in gastric cancer. These was a relationship between down-regulation of ASK1 and distant metastasis in gastric cancer.3 The expression of ASK1 and MMP-9 has a close correlation. It may be a mechanism of invasion and metastasis in gastric cancer in which absence of ASK1 contribute to the overexpression of MMP-9.