Expression of tight-junction-associated proteins in human gastric cancer: downregulation of claudin-4 correlates with tumor aggressiveness and survival

Background Claudin, occludin, and zonula occludens (ZO)-1 are known as tight-junction-associated proteins. The aim of this study was to examine the expression of these proteins in gastric carcinoma. Methods Gastric cancer tissues ( n = 124) were obtained from 124 patients who underwent gastrectomy a...

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Veröffentlicht in:Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2009-04, Vol.12 (1), p.43-51
Hauptverfasser: Ohtani, Satoshi, Terashima, Masanori, Satoh, Jun, Soeta, Nobutoshi, Saze, Zenichiroh, Kashimura, Seigo, Ohsuka, Fumihiko, Hoshino, Yutaka, Kogure, Michihiko, Gotoh, Mitsukazu
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Sprache:eng
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Zusammenfassung:Background Claudin, occludin, and zonula occludens (ZO)-1 are known as tight-junction-associated proteins. The aim of this study was to examine the expression of these proteins in gastric carcinoma. Methods Gastric cancer tissues ( n = 124) were obtained from 124 patients who underwent gastrectomy at our hospital between January 2000 and December 2004. The expression of the above tight-junction-associated proteins in carcinoma, normal mucosa, and metaplastic epithelium was examined using immunohistochemistry. In addition, the expression of claudin-4 mRNA was examined in fresh frozen tissue obtained from 34 patients. Results Significant correlations were seen between the expression of claudin-4, occludin, and ZO-1. In regard to claudin-4, significant correlations were seen between the expression of claudin-4 evaluated by immunohistochemistry and the expression of claudin-4 mRNA. Claudin-4 expression was significantly decreased in tumors with undifferentiated-type adenocarcinoma, advanced T stage, lymph node metastasis, and peritoneal metastasis. Occludin and ZO-1 expression was significantly decreased in tumors with undifferentiated-type adenocarcinoma. Overall survival was significantly shorter in patients with low claudin-4 expression. Cox multivariate analysis revealed that low claudin-4 expression was independently associated with significantly decreased overall survival. Conclusion Tight-junction-associated proteins, particularly claudin-4, may play important roles in determining invasiveness, metastatic potential, and survival in gastric cancer.
ISSN:1436-3291
1436-3305
DOI:10.1007/s10120-008-0497-0