Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer
Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer
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DOI：
10.1007/s10549-012-2314-z
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发表时间：
2012-12-01
影响因子：
3.8
通讯作者：
Yu, Herbert
中科院分区：
文献类型：
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作者：
Lu, Lingeng;Zhu, Gongjian;Yu, Herbert
大的非编码RNA HOTAIR，从HOXC 12的反义链转录，与多梳抑制复合物2（PRC 2）在基因活性的调节中相互作用。最近的研究表明，它可能对乳腺癌的进展和生存有影响。我们评估了原发性乳腺癌中HOTAIR的表达及其下游基因间CpG岛的甲基化状态，并研究了这些因素与临床和病理特征以及患者生存率的相关性。采用定量RT-PCR和甲基化特异性PCR分别检测348例原发性乳腺癌组织中HOTAIR的表达和DNA甲基化。HOTAIR表达和甲基化在组织中变化很大。DNA甲基化与HOTAIR表达呈正相关。甲基化与不利的疾病特征相关，而HOTAIR表达与临床或病理特征之间无显著相关性。在多变量，但不是在单变量，考克斯比例风险回归模型中，高HOTAIR表达的患者比低HOTAIR表达的患者复发和死亡的风险较低。这些结果表明，基因间DNA甲基化可能在调控HOTAIR表达方面具有重要的生物学意义，HOTAIR表达可能不是乳腺癌独立的预后指标，但需要进一步的独立研究验证。
Large noncoding RNA HOTAIR, transcribed from the antisense strand of HOXC12, interacts with Polycomb Repressive Complex 2 (PRC2) in the regulation of gene activities. Recent work suggests that it may have effects on breast cancer progression and survival. We evaluated HOTAIR expression and the methylation status of its downstream intergenic CpG island in primary breast cancers, and examined associations of these factors with clinical and pathologic features and patient survival. HOTAIR expression and DNA methylation were analyzed in tissue from 348 primary breast cancers with quantitative RT-PCR and methylation-specific PCR, respectively. HOTAIR expression and methylation varied widely in the tissues. A positive correlation was found between DNA methylation and HOTAIR expression. Methylation was associated with unfavorable disease characteristics, whereas no significant associations were found between HOTAIR expression and clinical or pathologic features. In multivariate, but not in univariate, Cox proportional hazard regression models, patients with high HOTAIR expression had lower risks of relapse and mortality than those with low HOTAIR expression. These findings suggest that the intergenic DNA methylation may have important biologic relevance in regulating HOTAIR expression, and that HOTAIR expression may not be an independent prognostic marker in breast cancer, but needs further validation in independent studies.