Claudin-4 is a member of the claudin family, a large family of transmembrane proteins that are essential in the formation and maintenance of tight junctions. Matrix metalloproteinase (MMP)-2 and -9 degrade type IV collagen of the extracellular matrix and basal membranes. Claudin-4 activates MMP-2, indicating that claudin-mediated increased cancer cell invasion may result from the activation of MMP proteins. In the present study, we used immunohistochemistry to examine the expression levels of claudin-4, MMP-2 and MMP-9 in 189 gastric cancer samples, and analyzed their correlation with tumor invasion, clinicopathologic parameters and clinical outcome. The relationship between claudin-4 expression and MMP-2 and -9 expression was also investigated. The expression of claudin-4 was found to be significantly higher in gastric cancer cases with advanced depth of wall invasion, lymph node metastasis, lymphatic invasion and higher TNM stage. Further analysis revealed claudin-4 expression to be significantly correlated with the expression of MMP-2 and -9. Kaplan-Meier survival analysis indicated that MMP-9 expression was correlated with poor prognosis. These results suggest that claudin-4 expression is associated with tumor invasion and with MMP-2 and -9 expression in gastric cancer. Additionally, MMP-9 expression was demonstrated to serve as a prognostic factor in patients with gastric cancer.

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