Identification of histone deacetylase 3 as a biomarker for tumor recurrence following liver transplantation in HBV-associated hepatocellular carcinoma.
Identification of histone deacetylase 3 as a biomarker for tumor recurrence following liver transplantation in HBV-associated hepatocellular carcinoma.
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鉴定组蛋白脱乙酰酶 3 作为 HBV 相关肝细胞癌肝移植后肿瘤复发的生物标志物
DOI：
10.1371/journal.pone.0014460
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发表时间：
2010-12-29
期刊：
影响因子：
3.7
通讯作者：
Zheng SS
中科院分区：
文献类型：
--
作者：
Wu LM;Yang Z;Zhou L;Zhang F;Xie HY;Feng XW;Wu J;Zheng SS
背景最近的研究表明，在某些人类肿瘤中，组蛋白I类脱乙酰酶的高表达水平与恶性表型和预后不良有关。然而，I类HDAC亚型在肝细胞癌中的表达模式和预后作用尚不清楚。方法/主要研究结果：采用免疫组织化学方法对43例接受肝移植治疗的乙肝病毒相关性肝细胞癌患者中I类HDAC亚型的表达模式和临床意义进行了研究。此外，通过用短干扰RNA敲除HDAC异构体来研究HDAC抑制对肝癌细胞行为的影响。HDAC1、HDAC2和HDAC3阳性率分别为51.2%、48.8%和32.6%。HDAC亚型的表达水平与肝细胞癌的增殖指数显著相关。Kaplan-Meier曲线显示，HDAC2或HDAC3的高表达水平显著降低了无复发生存率。COX比例风险模型分析显示，HDAC3过度表达是一个不利的独立预后因素(P = 为0.002；HR为3.907)。在体外，抑制HDAC2和HDAC3，而不是HDAC1，抑制肝癌细胞的增殖和侵袭力。结论HDAC3在调节肿瘤细胞增殖和侵袭中起重要作用，可作为预测肝移植后乙肝病毒相关性肝癌复发的候选生物标志物和潜在的治疗靶点。
Background Recent studies have shown that high expression levels of class I histone deacetylases (HDACs) correlate with malignant phenotype and poor prognosis in some human tumors. However, the expression patterns and prognostic role of class I HDAC isoforms in hepatocellular carcinoma (HCC) remain unclear. Methodology/Principal Findings The expression patterns and clinical significance of class I HDAC isoforms were assessed by immunohistochemistry in a cohort of 43 hepatitis B virus-associated HCC patients treated with liver transplantation. In addition, the effects of HDAC inhibition on HCC cell behavior were investigated by knockdown of the HDAC isoform with short interfering RNA. Class I HDACs were highly expressed in a subset of HCCs with positivity for HDAC1 in 51.2%, HDAC2 in 48.8%, and HDAC3 in 32.6% of cases. The expression levels of HDAC isoforms were significantly associated with the proliferation index of HCC. Kaplan-Meier curves showed that a high expression level of HDAC2 or HDAC3 implicated significantly reduced recurrence-free survival. Cox proportional hazards model analysis revealed HDAC3 overexpression was an unfavorable independent prognostic factor (P = 0.002; HR 3.907). In vitro, inhibition of HDAC2 and HDAC3, but not HDAC1, suppressed proliferation and the invasiveness of liver cancer cells. Conclusions/Significance Our findings demonstrate that HDAC3 plays a significant role in regulating tumor cell proliferation and invasion, and it could be served as a candidate biomarker for predicting the recurrence of hepatitis B virus-associated HCC following liver transplantation and a potential therapeutic target.
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影响因子：
3.5
作者：
Wu, L. M.;Zhang, F.;Zheng, S. S.
通讯作者：
Zheng, S. S.
影响因子：
4.8
作者：
Wilson, AJ;Byun, DS;Mariadason, JM
通讯作者：
Mariadason, JM
影响因子：
4.6
作者：
Spurling, Colleen C.;Godman, Cassandra A.;Giardina, Charles
通讯作者：
Giardina, Charles
DOI：
10.1016/s1383-5742(00)00027-2
发表时间：
2000-04-01
影响因子：
5.3
作者：
Wild, CP;Hall, AJ
通讯作者：
Hall, AJ
影响因子：
4.8
作者：
Weichert, Wilko;Denkert, Carsten;Kobel, Martin
通讯作者：
Kobel, Martin