多梳抑制复合物 2 的关键成分 EZH2/SUZ12/EED 的过表达作为胆管癌不良预后的标志物。
Overexpression of polycomb repressive complex 2 key components EZH2/SUZ12/EED as an unfavorable prognostic marker in cholangiocarcinoma.
机构信息
Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand; Biomedical Sciences, Graduate School, Khon Kaen University, Khon Kaen, 40002, Thailand.
Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
出版信息
Pathol Res Pract. 2019 Jul;215(7):152451. doi: 10.1016/j.prp.2019.152451. Epub 2019 May 13.
BACKGROUND
Cholangiocarcinoma (CCA) is a fatal liver cancer arising from bile duct epithelium. Polycomb repressive complex 2 (PRC2) is a histone methyltransferase enzyme that catalyzes trimethylation of histone H3 on lysine 27, resulting transcriptional gene silencing. The key components of PRC2 are EZH2, SUZ12 and EED, which EZH2 is a catalytic subunit. The defect of individual PRC2 components has been shown to enhance carcinogenesis and cancer progression. The aim of this study was to determine the expression of individual PRC2 components and evaluate its association with clinicopathological data in CCA patients.
METHODS
The expression of PRC2 components including EZH2, SUZ12 and EED was determined by immunohistochemistry in 40 CCA tissue samples.
RESULTS
The expression of EZH2 and SUZ12 in CCA tissue was significantly higher than that in adjacent non-cancerous tissue (P < 0.001). The high cytoplasmic EZH2 expression was significantly associated with short overall survival in CCA (P = 0.030). Interestingly, a combined high nuclear and cytoplasmic expression of EZH2 was found to be a worse prognostic marker for overall survival (P = 0.015). Moreover, combined high expression of EZH2 and SUZ12/EED was also associated with short overall survival (P < 0.05).
CONCLUSIONS
Our findings suggest that overexpression of the PRC2 key components especially EZH2 in both nucleus and cytoplasm can be potentially used as a prognostic marker for CCA.
背景
胆管癌（CCA）是一种源自胆管上皮的致命肝癌。多梳抑制复合物 2（PRC2）是一种组蛋白甲基转移酶，可催化组蛋白 H3 赖氨酸 27 的三甲基化，导致基因转录沉默。PRC2 的关键组成部分是 EZH2、SUZ12 和 EED，其中 EZH2 是催化亚基。单个 PRC2 成分的缺陷已被证明会增强致癌作用和癌症进展。本研究旨在确定 PRC2 成分的表达，并评估其与 CCA 患者临床病理数据的关联。
方法
通过免疫组织化学法检测 40 例 CCA 组织样本中 PRC2 成分（包括 EZH2、SUZ12 和 EED）的表达。
结果
CCA 组织中 EZH2 和 SUZ12 的表达明显高于相邻非癌组织（P<0.001）。细胞质中 EZH2 高表达与 CCA 患者总生存期缩短显著相关（P=0.030）。有趣的是，EZH2 的核质高表达联合被发现是总生存期的预后不良标志物（P=0.015）。此外，EZH2 和 SUZ12/EED 的联合高表达也与总生存期缩短相关（P<0.05）。
结论
我们的研究结果表明，PRC2 关键成分（尤其是核质中 EZH2）的过表达可能可用作 CCA 的预后标志物。
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