Concurrent activation of acetylation and tri-methylation of H3K27 in a subset of hepatocellular carcinoma with aggressive behavior.
Concurrent activation of acetylation and tri-methylation of H3K27 in a subset of hepatocellular carcinoma with aggressive behavior.
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DOI：
10.1371/journal.pone.0091330
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Fukayama M
中科院分区：
文献类型：
--
作者：
Hayashi A;Yamauchi N;Shibahara J;Kimura H;Morikawa T;Ishikawa S;Nagae G;Nishi A;Sakamoto Y;Kokudo N;Aburatani H;Fukayama M
分析组蛋白分子相同残基的乙酰化和三甲基化可能会识别出具有侵袭性行为的肝细胞癌（HCC）的一个亚群。在本研究中，我们检测了组蛋白H3上赖氨酸27的乙酰化和三甲基化（分别为H3K27ac和H3K27me3），因为已知这两种修饰对基因表达表现出相反的作用（增强和沉默）。用H3K27ac和H3K27me3特异性单克隆抗体对198例HCC患者的肿瘤和非肿瘤组织进行免疫染色。通过图像分析程序评估染色组织以生成组织学评分（h评分，范围0-300），该评分由阳性染色细胞的百分比乘以分类免疫组织化学标记强度（0-3）确定。HCC组织H3K27ac（156.7±86.8）和H3K27me3 h评分（151.8±78.1）明显高于背景肝（分别为40.3±33.0和64.7±45.6）（P均<0.001）。h评分高h3k27ac /高h3k27me3的病例（n = 54）与形态学分化差（P<0.01）、p53染色阳性（P<0.05）、预后差（P<0.01）有显著相关性。共聚焦显微镜显示这两种修饰在单个癌细胞中分离的核内定位：H3K27ac定位在中心常染色质区域，H3K27me3定位在外周异染色质区域。HCC细胞中H3K27位点的乙酰化和甲基化与p53异常有关。这些发现表明，图像分析仪辅助的H3K27ac和H3K27me3的h评分可识别HCC的侵袭性亚组，并可作为HCC的预后标志物。
Analysis of acetylation and tri-methylation of the same residue of histone molecules might identify a subset of hepatocellular carcinoma (HCC) with aggressive behavior. In the present study, we examined acetylation and tri-methylation of lysine 27 on histone H3 (H3K27ac and H3K27me3, respectively) because these two modifications are known to exhibit opposite effects (enhancing and silencing) on gene expression. Neoplastic and non-neoplastic tissues from 198 HCC cases were immunostained with specific monoclonal antibodies against H3K27ac and H3K27me3. The stained tissues were evaluated by an image analyzing program to generate histological scores (H-scores, range 0–300), which were determined by multiplying the percentage of positive-stained cells with the classified immunohistochemical marker intensity (0–3). HCC tissues showed significantly higher H3K27ac (156.7±86.8) and H3K27me3 H-scores (151.8±78.1) compared with the background liver (40.3±33.0 and 64.7±45.6, respectively) (both P<0.001). The cases with H-scores of high-H3K27ac/high-H3K27me3 (n = 54) showed significant correlation with poor differentiation of morphology (P<0.01) and p53-positive staining (P<0.05), and poor prognosis (P<0.01). Confocal microscopy revealed segregated intranuclear localization of both modifications in the individual cancer cells: H3K27ac localization in central euchromatin regions and H3K27me3 in peripheral heterochromatin regions. Concurrent acetylation and methylation at H3K27 occurs in HCC cells in association with p53 abnormalities. These findings demonstrate that image analyzer-assisted H-scores of H3K27ac and H3K27me3 identified an aggressive subgroup of HCC, and could serve as a prognostic marker for HCC.
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影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
11.2
作者：
Hoshida Y;Nijman SM;Kobayashi M;Chan JA;Brunet JP;Chiang DY;Villanueva A;Newell P;Ikeda K;Hashimoto M;Watanabe G;Gabriel S;Friedman SL;Kumada H;Llovet JM;Golub TR
通讯作者：
Golub TR
影响因子：
7.4
作者：
Li M;Luo RZ;Chen JW;Cao Y;Lu JB;He JH;Wu QL;Cai MY
通讯作者：
Cai MY
影响因子：
3.3
作者：
Chen, X;Cheung, ST;Brown, PO
通讯作者：
Brown, PO
影响因子：
82.9
作者：
Kononen, J;Bubendorf, L;Kallioniemi, OP
通讯作者：
Kallioniemi, OP