Enhancer of zeste homolog 2 (EZH2) regulates tumor angiogenesis and predicts recurrence and prognosis of intrahepatic cholangiocarcinoma
Enhancer of zeste homolog 2 (EZH2) regulates tumor angiogenesis and predicts recurrence and prognosis of intrahepatic cholangiocarcinoma
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DOI：
10.1016/j.hpb.2018.03.018
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发表时间：
2018-10-01
期刊：
影响因子：
2.9
通讯作者：
Baba, Hideo
中科院分区：
文献类型：
--
作者：
Nakagawa, Shigeki;Okabe, Hirohisa;Baba, Hideo
背景资料：zeste增强子同源物2（EZH 2）是多梳抑制复合物2（PRC 2）的催化亚基，并通过组蛋白甲基化介导的基因沉默来调节肿瘤恶性程度。本研究旨在探讨EZH 2在肝内胆管癌（intrahepatic cholangiocarcinoma，ICC）血管生成中的作用。我们还通过免疫组化（IHC）染色和体外基因沉默试验评估了47例ICC患者EZH 2和血管抑制素1（VASH 1）表达之间的相关性。结果：生物信息学分析显示，EZH 2与公共数据库中的多个血管生成基因集相关。EZH 2在体外测定和IHC研究中抑制VASH 1表达。EZH 2-high/VASH 1-low状态与低无病生存期（P = 0.019）和低总生存期（P = 0.0055）独立相关。结论：EZH 2高表达与肿瘤血管生成激活相关，EZH 2介导的血管生成通路的激活可预测ICC患者的预后。
Background: Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) and regulates tumor malignancy by gene silencing via histone methylation. In this study we investigate the role of EZH2 in angiogenesis of intrahepatic cholangiocarcinoma (ICC).Methods: The influence of EZH2 on tumor angiogenesis was examined by bioinformatics analysis of a public database. We also assessed the correlation between EZH2 and vasohibin 1 (VASH1) expression in 47 patients with ICC by immunohistochemical (IHC) staining and in vitro gene silencing assays. The prognostic significance of EZH2 and VASH1 expression by IHC was also examined in the ICC cohort.Results: Bioinformatics analysis showed that EZH2 was associated with several angiogenesis gene sets in the public database. EZH2 suppressed VASH1 expression in in vitro assays and IHC studies. EZH2-high/VASH1-low status was independently associated with poor disease-free survival (P = 0.019) and poor overall survival (P = 0.0055).Conclusion: The current study demonstrated that high EZH2 expression was associated with activation of tumor angiogenesis, and activation of the EZH2-mediated angiogenesis pathway predicted the prognosis of patients with ICC.