摘要
目的:本研究旨在利用不同的微阵列研究来识别扩张性心肌病(DCM)的常见基因表达信号。背景:在西方国家,DCM是心力衰竭的一个常见病因。虽然基因表达阵列已成为描述复杂疾病模式的强有力工具。
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.
