Integrated transcriptome and proteome profiling of human end-stage dilated cardiomyopathy identified 1262 differentially expressed genes and 269 proteins compared to non-failing controls, with 16 entities commonly altered across both platforms.
Case-Control (n=10)
No
p-value: p=<0.05
AIMS: The disease pathways leading to idiopathic dilated cardiomyopathy (DCM) are still elusive. The present study investigated integrated global transcriptional and translational changes in human DCM for disease biomarker discovery. METHODS: We used identical myocardial tissues from five DCM hearts compared to five non-failing (NF) donor hearts for both transcriptome profiling using the ABI high-density oligonucleotide microarrays and proteome expression with One-Dimensional Nano Acquity liquid chromatography coupled with tandem mass spectrometry on the Synapt G2 system. RESULTS: We identified 1262 differentially expressed genes (DEGs) and 269 proteins (DEPs) between DCM cases and healthy controls. Among the most significantly upregulated (>5-fold) proteins were GRK5, APOA2, IGHG3, ANXA6, HSP90AA1, and ATP5C1 (p< 0.01). On the other hand, the most significantly downregulated proteins were GSTM5, COX17, CAV1 and ANXA3. At least ten entities were concomitantly upregulated on the two analysis platforms: GOT1, ALDH4A1, PDHB, BDH1, SLC2A11, HSP90AA1, HSP90AB1, H2AFV, HSPA5 and NDUFV1. Gene ontology analyses of DEGs and DEPs revealed significant overlap with enrichment of genes/proteins related to metabolic process, biosynthetic process, cellular component organization, oxidative phosphorylation, alterations in glycolysis and ATP synthesis, Alzheimer's disease, chemokine-mediated inflammation and cytokine signalling pathways. CONCLUSION: The concomitant use of transcriptome and proteome expression to evaluate global changes in DCM has led to the identification of sixteen commonly altered entities as well as novel genes, proteins and pathways whose cardiac functions have yet to be deciphered. This data should contribute towards better management of the disease.
Çolak et al. (2016) conducted a case-control in End-Stage Dilated Cardiomyopathy (n=10). End-Stage Dilated Cardiomyopathy vs. Non-failing donor hearts was evaluated on Differentially expressed genes (DEGs) and proteins (DEPs) (p=<0.05). Integrated transcriptome and proteome profiling of human end-stage dilated cardiomyopathy identified 1262 differentially expressed genes and 269 proteins compared to non-failing controls, with 16 entities commonly altered across both platforms.