Aberrant differential expression of EZH2 and H3K27me3 in extranodal NK/T-cell lymphoma, nasal type, is associated with disease progression and prognosis
Aberrant differential expression of EZH2 and H3K27me3 in extranodal NK/T-cell lymphoma, nasal type, is associated with disease progression and prognosis
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EZH2 和 H3K27me3 在鼻型结外 NK/T 细胞淋巴瘤中的异常差异表达与疾病进展和预后相关
DOI：
10.1016/j.humpath.2018.08.025
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发表时间：
2019-01-01
期刊：
影响因子：
3.3
通讯作者：
Li, Ting
中科院分区：
文献类型：
--
作者：
Liu, Jumei;Liang, Li;Li, Ting
ZAST同源增强子2(EZH2)是一种H3K27特异性的组蛋白甲基转移酶，已被证明在包括淋巴瘤在内的各种人类癌症中经常过表达。在这里，我们研究了EZH2和H3K27me3在结外NK/T细胞淋巴瘤鼻型(ENKTL)中的表达和功能。纳米线分析结果表明，EZH2和相关的组蛋白H3家族是ENKTL组织中上调的基因。免疫组织化学结果显示EZH2和组蛋白(H3K27me3)中Lys-27的三甲基化在ENKTL中的高表达分别为55.2%和78.0%。EZH2型过表达与肿瘤细胞的高增殖(r=0.582，P=.000)、晚期(P=.012)和较差的总生存期(P=.016)显著相关。H3K27me3阳性表达与肿瘤细胞增殖率低(r=-0.623，P=0.036)、分期早(P=0.043)、总生存率高(P=0.020)相关。免疫组织化学显示EZH2和H3K27me3在临床标本中呈负相关(r=-0.652，P=0.002)。此外，3-去氮杂环素A抑制EZH2显著抑制肿瘤细胞的生长。有趣的是，药物抑制JAK3/STAT3通路有效地降低了NK/T肿瘤细胞株的EZH2和增强了H3K27me3。我们的数据提示EZH2和H3K27me3是ENKTL的重要预后标志物和潜在的治疗靶点。(C)2018 Elsevier Inc.保留所有权利。
Enhancer of zeste homolog 2 (EZH2), an H3K27-specific histone methyltransferase, has been shown to be frequently overexpressed in various human cancers including lymphoma. Here we investigate the expression and functionality of EZH2 and H3K27me3 in extranodal NK/T-cell lymphoma, nasal type (ENKTL). Results of NanoString analysis revealed that EZH2 and related histone H3 families were upregulated genes in ENKTL tissues. Results of immunohistochemistry demonstrated that EZH2 and trimethylation of Lys-27 in histone (H3K27me3) were highly expressed in 55.2% and 78.0% of patients with ENKTL, respectively. EZH2 overexpression was significantly associated with higher tumor cell proliferation (r = 0.582, P = .000), advanced stage (P = .012), and predicted poorer overall survival (P = .016) in ENKTL. H3K27me3-positive expression was correlated with lower tumor cell proliferation (r = -0.623, P = .036), earlier stage (P = .043), and predicted better overall survival (P = .020). In addition, EZH2 and H3K27me3 showed inverse correlations (r = -0.652, P = .002) in clinical samples by immunohisto chemistry. Furthermore, inhibition of EZH2 by 3-deazaneplanocin A significantly suppressed tumor cell growth. Interestingly, pharmacologic suppression of the JAK3/STAT3 pathway effectively reduced EZH2 and enhanced H3K27me3 in NK/T tumor cell lines. Our data suggest that EZH2 and H3K27me3 are important prognostic markers and potential therapeutic targets in ENKTL. (C) 2018 Elsevier Inc. All rights reserved.