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Claudin 1 的表达与β-catenin 相关,是胃癌预后不良的一个预后因素。

The expression of claudin 1 correlates with β-catenin and is a prognostic factor of poor outcome in gastric cancer.

机构信息

Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.

Department of Surgery, Department of Obstetrics and Gynecology, Women's Cancer Institute, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

出版信息

Int J Oncol. 2014 Apr;44(4):1293-301. doi: 10.3892/ijo.2014.2298. Epub 2014 Feb 12.

Abstract

Claudin 1 is one of the tight junction proteins, which are critical in the maintenance of epithelial integrity. Aberrant regulation of CLDN1 and its correlation with β-catenin have been discovered in malignant tumors. The present study aimed to investigate the expression profile and clinical relevance of CLDN1 and β-catenin. The protein levels of CLDN1 and β-catenin were examined using immunohistochemical staining. The characteristics of expression profile and prognostic value were analyzed using Pearson's χ² test and Kaplan-Meier analysis, respectively. β-catenin overexpression and knockdown were used to investigate its role in regulating CLDN1 expression. We showed that CLDN1 was overexpressed in intestinal-type, presence of lymph node metastasis, higher TNM stage in gastric cancer patients and correlated with decreased overall survival. The characteristics of CLDN1 expression were associated with that of β-catenin. CLDN1 and β-catenin showed similar prognostic value in intestinal-type gastric cancers. β-catenin knockdown and overexpression in cell models revealed a positive relation between CLDN1 and β-catenin. Our study demonstrated that CLDN1 is a biomarker for intestinal-type gastric cancer with shorter survival. The expression of CLDN1 was strongly associated with β-catenin in gastric cancer patients and a gastric cancer cell model.

摘要

Claudin 1 是紧密连接蛋白之一,对于维持上皮完整性至关重要。在恶性肿瘤中发现 CLDN1 的异常调节及其与β-catenin 的相关性。本研究旨在探讨 CLDN1 和β-catenin 的表达谱和临床相关性。使用免疫组织化学染色检测 CLDN1 和β-catenin 的蛋白水平。使用 Pearson's χ²检验和 Kaplan-Meier 分析分别分析表达谱和预后价值的特征。使用β-catenin 过表达和敲低来研究其在调节 CLDN1 表达中的作用。我们表明,CLDN1 在肠型、淋巴结转移存在、胃癌患者更高的 TNM 分期中过度表达,与总生存期缩短相关。CLDN1 表达的特征与β-catenin 的特征相关。CLDN1 和β-catenin 在肠型胃癌中具有相似的预后价值。细胞模型中的β-catenin 敲低和过表达揭示了 CLDN1 和β-catenin 之间存在正相关关系。我们的研究表明,CLDN1 是生存时间较短的肠型胃癌的生物标志物。CLDN1 在胃癌患者和胃癌细胞模型中的表达与β-catenin 密切相关。

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