Analysis of H3K27me3 expression and DNA methylation at CCGG sites in smoking and non-smoking patients with non-small cell lung cancer and their clinical significance.
Analysis of H3K27me3 expression and DNA methylation at CCGG sites in smoking and non-smoking patients with non-small cell lung cancer and their clinical significance.
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DOI：
10.3892/ol.2018.8100
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发表时间：
2018-05
期刊：
影响因子：
2.9
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Zhu K;Deng Y;Weng G;Hu D;Huang C;Matsumoto K;Nagayasu T;Koji T;Zheng X;Jiang W;Lin G;Cai Y;Weng G;Chen X
吸烟经常导致表观遗传改变，包括DNA甲基化和组蛋白修饰。分析吸烟对非小细胞肺癌(NSCLC)患者CCGG区DNA甲基化水平、组蛋白H3赖氨酸27位三甲基化(H3K27me3)和ZEST同源基因增强子2(EZH2)表达的影响及其相互作用。本研究共纳入42例非小细胞肺癌患者、22例腺癌患者和20例鳞癌患者。免疫组织化学方法检测H3K27me3、EZH2和增殖细胞核抗原的表达。通过DNA甲基化位点的组织内切酶连接检测来评估CCGG位点的DNA甲基化。采用末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记法检测不同吸烟状态患者癌组织的细胞凋亡指数。计算与不同吸烟状态相关的临床病理数据。与非吸烟者相比，吸烟者NSCLC的细胞凋亡指数显著降低(P<；0.05)，CCGG位点DNA甲基化水平降低，H3K27me3表达降低，EZH2表达升高(P<；0.05)。CCGG基因甲基化水平与Brinkman指数呈负相关(P=0.017)。此外，在大多数吸烟者中，H3K27me3和EZH2的表达水平之间存在平行关联，而在大多数非吸烟者中，存在不同的关联(P=0.015)。在大多数吸烟者中，增殖细胞核抗原和EZH2的表达水平之间存在不同的关联；然而，在大多数非吸烟者中，存在平行关联(P=0.048)。此外，在大多数吸烟者中，CCGG甲基化比率与H3K27me3的免疫组织化学表达之间存在平行关联，而在大多数非吸烟者中存在不同的关联(P=0.049)。结论：不同吸烟状态的非小细胞肺癌患者表现出不同的表观遗传学特征。此外，CCGG位点的DNA甲基化水平可能具有确定H3K27me3、EZH2和增殖细胞核抗原表达水平之间的关联的能力。
Smoking frequently leads to epigenetic alterations, including DNA methylation and histone modifications. The effect that smoking has on the DNA methylation levels at CCGG sites, the expression of trimethylation of histone H3 at lysine 27 (H3K27me3) and enhancer of zeste homolog 2 (EZH2), and their interactions in patients with non-small cell lung cancer (NSCLC) were analyzed. There were a total of 42 patients with NSCLC, 22 with adenocarcinomas and 20 with squamous cell carcinomas enrolled in the present study. Expression of H3K27me3, EZH2 and proliferating cellular nuclear antigen (PCNA) were immunohistochemically detected. DNA methylation at CCGG sites was evaluated via histoendonuclease-linked detection of DNA methylation sites. The apoptotic index of cancerous tissues obtained from patients of different smoking statuses was evaluated via the terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling method. The association with clinicopathological data was calculated relative to different smoking statuses. Compared with the non-smokers, smokers with NSCLC exhibited a significantly lower apoptotic index (P<0.05), and frequently had a lower level of DNA methylation at CCGG sites, lower H3K27me3 expression and a higher EZH2 expression (P<0.05). DNA methylation levels at CCGG sites were negatively correlated to the Brinkman index (P=0.017). Furthermore, there was a parallel association between the H3K27me3 and EZH2 expression levels in the majority of smokers, whereas in the majority of non-smokers, there was a diverging association (P=0.015). There was a diverging association between the PCNA and EZH2 expression levels in the majority of smokers; however, in the majority of non-smokers, there was a parallel association (P=0.048). In addition, the association between the CCGG methylation ratio and immunohistochemical expression of H3K27me3 was a parallel association in the majority of smokers, while in the majority of non-smokers there was a diverging association (P=0.049). Conclusively, patients with NSCLC and different smoking statuses exhibit different epigenetic characteristics. Additionally, DNA methylation levels at the CCGG sites may have the ability to determine associations between the expression levels of H3K27me3, EZH2 and PCNA.
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影响因子：
6.6
作者：
Bjaanæs MM;Fleischer T;Halvorsen AR;Daunay A;Busato F;Solberg S;Jørgensen L;Kure E;Edvardsen H;Børresen-Dale AL;Brustugun OT;Tost J;Kristensen V;Helland Å
通讯作者：
Helland Å
影响因子：
2
作者：
Usemann, Jakob;Ernst, Thomas;Seeger, Karl
通讯作者：
Seeger, Karl
影响因子：
2.4
作者：
Ellinger, Joerg;Kahl, Philip;Rogenhofer, Sebastian
通讯作者：
Rogenhofer, Sebastian
影响因子：
4.4
作者：
Sundar, Isaac K.;Nevid, Michael Z.;Friedman, Alan E.;Rahman, Irfan
通讯作者：
Rahman, Irfan
DOI：
10.1083/jcb.119.3.493
发表时间：
1992-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gavrieli Y;Sherman Y;Ben-Sasson SA
通讯作者：
Ben-Sasson SA