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 Andreas S. Barth, Ruprecht Kuner, Andreas Buness, Markus Ruschhaupt, Sylvia Merk, Ludwig Zwermann, Stefan Kääb, Eckart Kreuzer, Gerhard Steinbeck, Ulrich Mansmann, Annemarie Poustka, Michael Nabauer, Holger Sültmann Although microarrays have emerged as a powerful tool for delineating complex disease patterns, differences in platform technology, tissue heterogeneity, and small sample sizes hamper a comprehensive interpretation of microarray studies in heart failure. Therefore, we performed 2 cDNA and oligonucleotide microarray studies with septal and left ventricular tissue from nonfailing and DCM hearts (each n = 20). Immune response processes displayed the most pronounced regulation on both microarray platforms. Furthermore, a robust set of 27 genes was identified that classified DCM and NF samples in our own microarray studies as well as in 2 additional publicly available datasets (total of 108 samples) with >90% accuracy. This study was designed to identify a common gene expression signature in dilated cardiomyopathy (DCM) across different microarray studies. 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. 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. 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. For the first time, independent microarray datasets pointed to significant invol