Identification of a common gene expression signature in dilated cardiomyopathy across independent microarray studies.
OBJECTIVE
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.
Barth
Andreas S
AS
Department of Medicine I, University Hospital Grosshadern, Munich, Germany. andreas.barth@med.uni-muenchen.de
Kuner
Ruprecht
R
Buness
Andreas
A
Ruschhaupt
Markus
M
Merk
Sylvia
S
Zwermann
Ludwig
L
Kääb
Stefan
S
Kreuzer
Eckart
E
Steinbeck
Gerhard
G
Mansmann
Ulrich
U
Poustka
Annemarie
A
Nabauer
Michael
M
Sültmann
Holger
H
D000917:Antibody Formation / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000503:physiopathology; D018450:Disease Progression; D015536:Down-Regulation; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis