Identification of a common gene expression signature in dilated cardiomyopathy across independent microarray studies
Identification of a common gene expression signature in dilated cardiomyopathy across independent microarray studies
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DOI：
10.1016/j.jacc.2006.07.026
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发表时间：
2006-10-17
影响因子：
24
通讯作者：
Sueltmann, Holger
中科院分区：
文献类型：
--
作者：
Barth, Andreas S.;Kuner, Ruprecht;Sueltmann, Holger
目的 本研究旨在通过不同的微阵列研究鉴定扩张型心肌病 (DCM) 的常见基因表达特征。背景扩张型心肌病是西方国家心力衰竭的常见原因。尽管基因表达芯片已成为描绘复杂疾病模式的强大工具，但平台技术的差异、组织异质性和小样本量掩盖了潜在的病理生理事件，并妨碍了对心力衰竭不同微阵列研究的全面解释。 方法我们通过进行两项基于 cDNA 和短寡核苷酸的全基因组表达研究来解释组织异质性和技术方面 微阵列平台包含来自非衰竭 (NF) (n 20) 和 DCM (n = 20) 心脏的独立隔膜和左心室组织样本。 结果 cDNA 和寡核苷酸微阵列之间的主要基因本体分类结果一致。值得注意的是，免疫反应过程在两种微阵列类型上表现出最明显的下调，将这种功能基因类别与终末期 DCM 的发病机制联系起来。此外，在我们的 cDNA 和寡核苷酸微阵列研究以及 2 个公开数据集的总共 108 个心肌样本中，确定了一组强大的 27 个基因，对 DCM 和 NF 样本进行分类的准确度 > 90%。 结论 独立的微阵列数据集首次表明免疫反应过程在终末期 DCM 中具有重要作用。此外，基于 4 个独立的微阵列数据集，我们提出了 DCM 的强大基因表达特征，鼓励未来在心力衰竭患者管理中实施疾病生物标志物的前瞻性研究。
OBJECTIVES This study was designed to identify a common gene expression signature in dilated cardiomyopathy (DCM) across different microarray studies.BACKGROUND Dilated cardiomyopathy is a common cause of heart failure in Western countries. Although gene expression arrays have emerged as a powerful tool for delineating complex disease patterns, differences in platform technology, tissue heterogeneity, and small sample sizes obscure the underlying pathophysiologic events and hamper a comprehensive interpretation of different microarray studies in heart failure.METHODS We accounted for tissue heterogeneity and technical aspects by performing 2 genome-wide expression studies based on cDNA and short-oligonucleotide microarray platforms which comprised independent septal and left ventricular tissue samples from nonfailing (NF) (n 20) and DCM (n = 20) hearts.RESULTS Concordant results emerged for major gene ontology classes between cDNA and oligonucleotide microarrays. Notably, immune response processes displayed the most pronounced down-regulation on both microarray types, linking this functional gene class to the pathogenesis of end-stage DCM. Furthermore, a robust set of 27 genes was identified that classified DCM and NF samples with > 90% accuracy in a total of 108 myocardial samples from our cDNA and oligonucleotide microarray studies as well as 2 publicly available datasets.CONCLUSIONS For the first time, independent microarray datasets pointed to significant involvement of immune response processes in end-stage DCM. Moreover, based on 4 independent microarray datasets, we present a robust gene expression signature of DCM, encouraging future prospective studies for the implementation of disease biomarkers in the management of patients with heart failure.