Integrated microarray analysis to identify potential biomarkers and therapeutic targets in dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a primary cardiomyopathy with high mortality. The aim of the present study was to identify the related genes in DCM. The four expression profiles (GSE17800, GSE21610, GSE42955 and GSE79962) downloaded from the Gene Expression Omnibus (GEO) database were analyzed using RankProd and metaMA R packages to identify differentially expressed genes (DEGs). DEGs were uploaded to the Database for Annotation, Visualization and Integrated Discovery (DAVID), for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A protein-protein interaction (PPI) network of the DEGs was constructed using the STRING database. In addition, hub genes were identified using the Cytoscape plugin cytoHubba. A mouse DCM model, which established via intraperitoneal injection with doxorubicin (DOX), was used to validate the hub genes. A total of 898 DEGs were identified across the four microarrays. Furthermore, GO analysis demonstrated that these DEGs were mainly enriched in cell adhesion, negative regulation of cell proliferation, negative regulation of apoptotic process and potassium ion transport. In addition, KEGG analysis revealed that DEGs were mainly enriched in the ECM-receptor interaction, the p53 signaling pathway, cardiac muscle contraction and the hypoxia-inducible factor signaling pathway. Proenkephalin (PENK), chordin like 1 (CHRDL1), calumenin (CALU), apolipoprotein L1, insulin-like growth factor binding protein 3 (IGFBP3) and ceruloplasmin (CP) were identified as hub genes in the PPI network. Furthermore, the expression levels of PENK, CHRDL1, IGFBP3, CP and CALU in hearts with DCM were validated using a mouse model. In conclusion, the present study identified six hub genes related to DCM. Therefore, the present results may provide a potential mechanism for DCM involving these hub genes, which may serve as biomarkers for screening and diagnosis in the clinic.