ZEB1 expression is associated with prognosis of intrahepatic cholangiocarcinoma
ZEB1 expression is associated with prognosis of intrahepatic cholangiocarcinoma
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DOI：
10.1136/jclinpath-2015-203115
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发表时间：
2016-07-01
影响因子：
3.4
通讯作者：
Sakamoto, Naoya
中科院分区：
文献类型：
--
作者：
Terashita, Katsumi;Chuma, Makoto;Sakamoto, Naoya
背景/目的肝内胆管细胞癌（Intrahepatic cholangiocarcinoma，ICC）是最具侵袭性的恶性肿瘤之一，因此寻找ICC的分子靶点是一个重要的研究课题。锌指E-box结合同源框1（ZEB 1）是上皮-间质转化（EMT）的关键诱导物。本研究的目的是阐明ZEB 1在ICC中的临床意义以及ZEB 1表达与EMT相关蛋白之间的关系。方法采用免疫组化方法检测102例ICC标本中EMT相关蛋白ZEB 1、vimentin和E-cadherin的表达。结果ZEB 1和波形蛋白在46.1%和43.1%的肿瘤中表达，E-cadherin在44.1%的肿瘤中表达缺失。ZEB 1表达与E-钙粘蛋白表达呈显著负相关（p=0.004），与波形蛋白表达呈正相关（p=0.022）。ZEB 1表达的改变与肿瘤的侵袭性特征相关，包括晚期肿瘤分期（p=0.037）、未分化型组织学（p=0.017）、淋巴结转移（p=0.024）和门静脉浸润（p=0.037）。此外，高ZEB 1表达患者的总生存率显著低于低ZEB 1表达患者（p=0.027）。Kaplan-Meier分析还确定了E-cadherin表达（p=0.041）和波形蛋白表达（p=0.049）作为预后指标的总survival.Conclusions ZEB 1表达与ICC患者的肿瘤进展和预后不良，通过与波形蛋白和E-cadherin呈负相关。ZEB 1表达与预后不良相关，可能是治疗ICC的一个有吸引力的靶点。
Background/Aim Intrahepatic cholangiocarcinoma (ICC) is one of the most aggressive malignant tumours, so the identification of molecular targets for ICC is an important issue. Zinc finger E-box binding homeobox 1 (ZEB1) is a key inducer of epithelial-mesenchymal transition (EMT). The aim of the present study was to clarify the clinical significance of ZEB1 in ICC and the associations between ZEB1 expression and EMT-related proteins.Methods We immunohistochemically examined the expression of EMT-related proteins, namely ZEB1, vimentin and E-cadherin, in ICC specimens from 102 patients. The clinicopathological and prognostic values of these markers were evaluated.Results ZEB1 and vimentin were expressed in 46.1% and 43.1% of tumours, respectively, and E-cadherin expression was lost in 44.1% of tumours. ZEB1 expression showed a significant inverse correlation with E-cadherin expression (p=0.004) and a positive correlation with vimentin expression (p=0.022). Altered expression of ZEB1 was associated with aggressive tumour characteristics, including advanced tumour stage (p=0.037), undifferentiated-type histology (p=0.017), lymph node metastasis (p=0.024) and portal vein invasion (p=0.037). Moreover, overall survival rates were significantly lower for patients with high ZEB1 expression than for patients with low ZEB1 expression (p=0.027). Kaplan-Meier analysis also identified E-cadherin expression (p=0.041) and vimentin expression (p=0.049) as prognostic indicators for overall survival.Conclusions ZEB1 expression is associated with tumour progression and poor prognosis in patients with ICC through positive correlations with vimentin and negative correlations with E-cadherin. ZEB1 expression is associated with a poor prognosis and might be an attractive target for the treatment of ICC.