Clinical Research
Heart Failure
Identification of a Common Gene Expression Signature in Dilated Cardiomyopathy Across Independent Microarray Studies

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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.

Abbreviations and Acronyms

DCM
dilated cardiomyopathy
GO
Gene Ontology
ICM
ischemic cardiomyopathy
NF
nonfailing

Cited by (0)

Supported by a grant from the German Federal Ministry for Education and Research supporting the German National Genome Research Network (BMBF-grant 01GS0109, NGFN grant 01GR0101, and NGFN grant 01GR0459) and a grant from the Deutsche Forschungsgemeinschaft (DFG grant BA 3341/1-1). Affymetrix data were generated and analyzed in the framework of a research collaboration with Aventis Pharma Deutschland. Drs. Barth, Kuner, Nabauer, and Sültmann contributed equally to this work.