Cluster Analysis of Claudin-1 and-4, E-Cadherin, and β-Catenin Expression in Colorectal Cancers
Cluster Analysis of Claudin-1 and-4, E-Cadherin, and β-Catenin Expression in Colorectal Cancers
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DOI：
10.1002/jso.21854
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发表时间：
2011-06-01
影响因子：
2.5
通讯作者：
Yao, Takashi
中科院分区：
文献类型：
--
作者：
Matsuoka, Takashi;Mitomi, Hiroyuki;Yao, Takashi
背景和目标：由密蛋白和钙粘蛋白/连环蛋白复合物介导的细胞间粘附是上皮完整性和分化的先决条件，并且已被认为在癌症中经常受到干扰。方法：采用免疫组化方法检测156例大肠癌组织中claudin-1、claudin-4、E-cadherin和beta-catenin的表达，并分析其与大肠癌临床病理特征的关系。表达减少与肿瘤分化差（claudin-1，P = 0.035; claudin-4，P = 0.011; E-cadherin，P < 0.001;膜β-catenin，P = 0.002）、晚期TNM分期（claudin-1，P = 0.002; claudin-4，P = 0.008）和预后差相关。多变量分析显示，侵袭性前沿E-cadherin（P < 0.001）和β-catenin（P = 0.048）表达降低是生存期短的独立预测因子。分层聚类分析确定了三个不同的组，具有良好的，中等的，和不良的预后，具有独立的生存结果的多变量分析（良好或中等与差：风险比，2.66; 95%置信区间，1.54-4.60; P < 0.001）。特异性标志物谱在此被确定为独立的预后指标。外科肿瘤学杂志2011;103：674-686。(C)2011 Wiley-Liss，Inc.
Background and Objectives: Intercellular adhesion mediated by the claudin and cadherin/catenin complex is a prerequisite for epithelial integrity and differentiation, and has been suggested to be frequently disturbed in cancers. The aim of this study was to assess the relationship between such abnormality and clinicopathological features of colorectal carcinomas.Methods: Immunohistochemical analysis of claudin-1 and -4, E-cadherin, and beta-catenin was performed on a series of 156 cases.Results: Significant positive associations (P < 0.05-0.001) were found with immunoreactivity for each except nuclear beta-catenin. Reduced expression was correlated with poor tumor differentiation (claudin-1, P = 0.035; claudin-4, P = 0.011; E-cadherin, P < 0.001; membranous beta-catenin, P = 0.002), an advanced TNM stage (claudin-1, P = 0.002; claudin-4, P = 0.008), and a poor prognosis. On multivariate analysis, reduced expression of E-cadherin (P < 0.001) and beta-catenin (P = 0.048) at invasive fronts proved to be an independent predictor of short survival. Hierarchical cluster analysis identified three distinct groups with a good, intermediate, and poor prognosis, having an independent survival outcome by multivariate analysis (good or intermediate vs. poor: hazard ratio, 2.66; 95% confidence interval, 1.54-4.60; P < 0.001).Conclusions: Disruption of cell adhesion molecules correlates with tumor differentiation and progression in colorectal carcinomas. Specific marker profiles were identified here as independent prognostic indicators. J. Surg. Oncol. 2011;103:674-686. (C) 2011 Wiley-Liss, Inc.