Ezrin protein overexpression predicts the poor prognosis of pancreatic ductal adenocarcinomas
Ezrin protein overexpression predicts the poor prognosis of pancreatic ductal adenocarcinomas
复制标题
DOI：
10.1016/j.yexmp.2014.11.003
复制
发表时间：
2015-02-01
影响因子：
3.6
通讯作者：
Liu, Shuangping
中科院分区：
文献类型：
--
作者：
Piao, Junjie;Liu, Shusen;Liu, Shuangping
埃兹林埃兹蛋白/根蛋白/膜突蛋白（ERM）蛋白家族的成员，在肿瘤转移中起重要作用。越来越多的研究表明，人类ezrin的高表达水平与许多人类恶性肿瘤相关。本研究旨在探讨ezrin蛋白在胰腺导管腺癌（PDAC）中的表达及其临床病理意义，并进一步探讨其作为PDAC潜在生物标志物和治疗靶点的作用。对106例PDAC组织样本和37例相邻和21例正常胰腺组织样本进行ezrin蛋白的免疫组织化学（IHC）染色。此外，使用免疫荧光（IF）染色观察Ezrin蛋白在Panc-1 PDAC细胞系中的定位。采用卡方检验评估ezrin过表达与PDAC临床病理特征的相关性，采用对数秩检验分析生存曲线的差异。结果表明，Ezrin蛋白在PDAC细胞中广泛分布于胞浆和胞膜，但部分病例呈胞膜染色。Ezrin蛋白在PDAC中的阳性表达率为82.1%（87/106），显著高于癌旁胰腺组织（37.8%，14/37）和正常胰腺组织（19.0%，4/21）。Ezrin的过表达与肿瘤体积较大、淋巴结转移阳性、临床分期较晚密切相关。而与患者年龄、性别、分化程度、Ki-67表达指数、胰腺钙化点无关。生存分析显示ezrin高表达组患者的总生存率明显低于ezrin低表达组。重要的是，进一步分析使用考克斯比例风险回归模型显示，高ezrin表达出现作为一个显着的独立危险因素的总生存率的PDAC沿着与淋巴结转移和TNM分期。结论ezrin蛋白在PDAC的发生发展中起重要作用，ezrin蛋白的过度表达可能是PDAC的一个有用的预后指标。(C)2014爱思唯尔公司All rights reserved.
Ezrin. a member of the ezrin/radixin/moesin (ERM) protein family, plays an important role in tumor metastasis. Accumulating studies demonstrated that a high expression level of human ezrin has been correlated with numerous human malignancies. This study was aimed to explore the clinicopathological significance of ezrin protein expression in pancreatic ductal adenocarcinomas (PDAC), and to further identify its role as a potential biomarker and therapeutic target of PDAC. Immunohistochemical (IHC) staining of ezrin protein was performed on 106 PDAC tissue samples and 37 adjacent and 21 normal pancreatic tissue samples. Additionally, localization of ezrin protein in Panc-1 PDAC cell line was observed using immunofluorescence (IF) staining. The correlation between ezrin overexpression and the clinicopathological features of PDAC was evaluated using Chi-square test, and differences in survival curves were analyzed using log-rank tests. In results, ezrin protein is widely distributed in the cytoplasm and membrane of PDAC cells by IHC and IF staining, but some cases showed a cell membrane staining pattern. The positive rate of ezrin protein expression was 82.1% (87/106) in PDAC, which was significantly higher than it in either adjacent pancreatic tissues (37.8%, 14/37) or normal pancreatic tissues (19.0%, 4/21). Overexpression of ezrin was closely related with larger tumor size, positive lymph node metastasis and advanced clinical stage. However, it was not correlated with patient age, gender, differentiation, Ki-67 expression index, and pancreas calcification point. Survival analysis showed that patients with ezrin high expression level had significantly lower overall survival rate than that with ezrin low expression level. Importantly, further analysis using a Cox proportional hazard regression model revealed that high ezrin expression emerged as a significant independent hazard factor for overall survival rates of patients with PDAC along with lymph node metastasis and TNM stage. In conclusion, ezrin protein played an important role in the progression of PDAC, and the overexpression of ezrin protein might be a useful prognostic marker of PDAC. (C) 2014 Elsevier Inc. All rights reserved.