Claudin-4 expression is associated with tumor invasion, MMP-2 and MMP-9 expression in gastric cancer

Hwang,Tsann-Long; Lee,Li-Yu; Wang,Chee-Chan; Liang,Ying; Huang,Shu-Fang; Wu,Chi-Ming

doi:10.3892/etm.2010.116

Claudin-4 expression is associated with tumor invasion, MMP-2 and MMP-9 expression in gastric cancer

Authors:
- Tsann-Long Hwang
- Li-Yu Lee
- Chee-Chan Wang
- Ying Liang
- Shu-Fang Huang
- Chi-Ming Wu
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Affiliations: Department of Surgery, Chang Gung Memorial Hospital, Vanung University, Taiwan, R.O.C., Department of Pathology, Chang Gung Memorial Hospital, Vanung University, Taiwan, R.O.C., Department of Cosmetic Science, Vanung University, Taiwan, R.O.C., Graduate Institute of Basic Medical Science, Chang Gung University, Tao-Yuan, Taiwan, R.O.C.
Published online on: July 12, 2010 https://doi.org/10.3892/etm.2010.116
Pages: 789-797

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Abstract

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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