Reduced expression of class II histone deacetylase genes is associated with poor prognosis in lung cancer patients
Reduced expression of class II histone deacetylase genes is associated with poor prognosis in lung cancer patients
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DOI：
10.1002/ijc.20395
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发表时间：
2004-10-20
影响因子：
6.4
通讯作者：
Takahashi, T
中科院分区：
文献类型：
--
作者：
Osada, H;Tatematsu, Y;Takahashi, T
HDAC基因被认为通过调节染色质结构参与基因表达，染色质结构的改变可能导致癌症中的异常基因沉默。为了阐明HDAC基因在肿瘤发生和发展过程中的可能作用，我们研究了它们的表达及其对临床特征的影响。采用实时荧光定量RTPCR方法检测72例NSCLC患者癌组织中HDAC I类和II类基因的表达水平。其与临床病理特征的关系进行了统计学研究。每个II类HDAC基因表达的减少与不良预后显著相关，并且是不良预后的独立预测因子。在所有基因中，HDAC 10是预后不良的最强预测因子。系统聚类分析结果显示，根据Ⅰ类和Ⅱ类HDAC基因的表达水平，肺癌组织可分为3组。Ⅱ类HDACs表达降低组预后差。这些结果表明，II类HDAC可能抑制关键基因，这些基因的低表达可能在肺癌进展中发挥作用。聚类分析的结果表明，第二类HDAC基因可能是由一个类似的机制调节和失调在癌症的发展。(C)2004 Wiley-Liss，Inc.
HDAC genes are thought to be involved in gene expression through the regulation of chromatin structure, alterations of which may cause abnormal gene silencing in cancers. To clarify the possible role of HDAC genes during tumor development and progression, we studied their expression and influence on clinical features. Expression levels of HDAC class I and class II genes in cancer tissues resected from 72 patients with NSCLC were measured with real-time RTPCR. Their association with clinicopathologic features was statistically investigated. Reduced expression of each class II HDAC gene was significantly associated with poor prognosis and an independent predictor of poor prognosis. Of all the genes, HDAC10 was the strongest predictor of poor prognosis. Hierarchical clustering analysis showed that lung cancer tissues could be divided into 3 groups based on the expression level of class I and class II HDAC genes. The group with reduced expression of class II HDACs showed poor prognosis. These results suggest that class II HDACs may repress critical genes and that low expression of these genes may play a role in lung cancer progression. Results of clustering analyses imply that class II HDAC genes may be regulated by a similar mechanism and deregulated during cancer development. (C) 2004 Wiley-Liss, Inc.