The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma
The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma
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DOI：
10.1002/cncr.20917
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发表时间：
2005-04-01
期刊：
影响因子：
6.2
通讯作者：
Hershko, DD
中科院分区：
文献类型：
--
作者：
Shapira, M;Ben-Izhak, O;Hershko, DD
背景：细胞周期抑制蛋白p27（kip1）的缺失与结直肠癌的不良预后相关。p27（kip1）水平的降低是蛋白酶体依赖性降解增加的结果，由其特异性泛素连接酶亚基S期激酶蛋白（Skp）2和细胞周期蛋白依赖性激酶亚基（Cks）1介导和限速。最近，Skp2和Cks1的表达被发现在一些结直肠癌中增加，但其作为预后标志物的潜在作用是未知的。本研究旨在评估Skp2和Cks1在结直肠癌中的预后价值。材料和方法：采用免疫组织化学方法，使用高度特异性抗体对80例结直肠癌患者福尔马林固定、石蜡包埋的组织切片进行Skp2、Cks1和p27（Kip1）的表达检测。Skp2和Cks1的过表达与p27（kip1）的缺失和肿瘤分化的丧失密切相关。在表达高Skp2或Cks1水平的患者中观察到总生存率显著降低，特别是II期和III期疾病患者。每种蛋白质提供了显着的额外的预后信息，由疾病分期，肿瘤分级，或p27（kip1）expressions.CONCLUSIONS：结果表明，Skp2或Cks1的过度表达与不良预后密切相关，因此可以作为预后指标，在结直肠癌的总生存率。(c)2005年美国癌症协会。
BACKGROUND: Loss of the cell-cycle inhibitory protein p27(kip1) is associated with poor prognosis in colorectal carcinoma. The decrease in p27(kip1) levels is the result of increased proteasome-dependent degradation, mediated and rate-limited by its specific ubiquitin ligase subunits S-phase kinase protein (Skp) 2 and cyclin-dependent kinase subunit (Cks) 1. Recently, Skp2 and Cks1 expression were found to be increased in some colorectal carcinomas, but their potential role as prognostic markers for survival is unknown. The present study was undertaken to assess the prognostic value of both Skp2 and Cks1 in colorectal carcinoma.MATERIALS AND METHODS: The expression of Skp2, Cks1, and p27(Kip1) was examined by immunohistochemistry using highly specific antibodies on formalin-fixed, paraffin-embedded tissue sections from 80 patients with colorectal carcinoma.RESULTS: Overexpression of Skp2 and Cks1 strongly correlated with loss of p27(kip1) and loss of tumor differentiation. A significant decrease in overall survival was observed in patients expressing high Skp2 or Cks1 levels, and in particular, patients with Stage II and III disease. Each protein provided significant additional prognostic information to that given by disease stage, tumor grade, or p27(kip1) expression.CONCLUSIONS: Results suggest that overexpression of Skp2 or Cks1 is strongly associated with poor prognosis and may thus be used as prognostic markers for overall survival in colorectal carcinoma. (c) 2005 American Cancer Society.