Piao Junjie, Liu Shusen, Xu Yunjie, Wang Changan, Lin Zhenhua, Qin Yunzhi, Liu Shuangping
Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji 133002, Jilin, China.
Department of Surgery, The Second Hospital of Jilin University, Changchun 130041, China.
Exp Mol Pathol. 2015 Feb;98(1):1-6. doi: 10.1016/j.yexmp.2014.11.003. Epub 2014 Nov 5.
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.
埃兹蛋白是埃兹蛋白/根蛋白/膜突蛋白(ERM)家族的成员之一,在肿瘤转移中起重要作用。越来越多的研究表明,人类埃兹蛋白的高表达水平与多种人类恶性肿瘤相关。本研究旨在探讨埃兹蛋白在胰腺导管腺癌(PDAC)中表达的临床病理意义,并进一步确定其作为PDAC潜在生物标志物和治疗靶点的作用。对106例PDAC组织样本、37例癌旁胰腺组织样本和21例正常胰腺组织样本进行了埃兹蛋白的免疫组织化学(IHC)染色。此外,采用免疫荧光(IF)染色观察埃兹蛋白在Panc-1 PDAC细胞系中的定位。采用卡方检验评估埃兹蛋白过表达与PDAC临床病理特征之间的相关性,采用对数秩检验分析生存曲线的差异。结果显示,通过IHC和IF染色,埃兹蛋白在PDAC细胞的细胞质和细胞膜中广泛分布,但部分病例呈现细胞膜染色模式。埃兹蛋白在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)。埃兹蛋白的过表达与肿瘤较大、淋巴结转移阳性及临床分期较晚密切相关。然而,它与患者年龄、性别、分化程度、Ki-67表达指数及胰腺钙化点无关。生存分析表明,埃兹蛋白高表达水平的患者总生存率显著低于埃兹蛋白低表达水平的患者。重要的是,使用Cox比例风险回归模型进行的进一步分析显示,埃兹蛋白高表达与淋巴结转移及TNM分期一样,是PDAC患者总生存率的一个显著独立危险因素。总之,埃兹蛋白在PDAC进展中起重要作用,埃兹蛋白的过表达可能是PDAC有用的预后标志物。