AUTHOR=Wei Ying , Cao Hao , Peng Yuan-Yi , Zhang Bo 

TITLE=Alterated gene expression in dilated cardiomyopathy after left ventricular assist device support by bioinformatics analysis

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1013057

DOI=10.3389/fcvm.2023.1013057

ISSN=2297-055X

ABSTRACT=Heart transplantation is the best treatment for end-stage dilated cardiomyopathy（DCM）. Left Ventricular assist device (LVAD) support is becoming more prevalent and may delay heart transplantation. The gene expression of the left ventricular myocardium usually changes following LVAD implantation. In this study, we aimed to identify potential biomarkers to determine the prognosis of patients with DCM after receiving LVAD support.
Methods We extracted microarray datasets from Gene Expression Omnibus (GEO), including GSE430 and GSE21610. There are 28 paired DCM samples in the GSE430 and GSE21610 profile. Differentially expressed genes (DEGs) were identified at LVAD implantation and heart transplantation. DEGs were annotated according to Gene Ontology (GO) and analyzed according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. An interaction network of protein-proteins (PPI) was constructed. The top ten crucial genes were predicted using the Cytoscape plugin CytoHubba in conformity with the network degree algorithm. The levels of gene expression and the diagnostic value of crucial genes were confirmed in the clinic datasets. 
Results The 28 DEGs were clustered into the GSE datasets. GO annotations and KEGG pathway enrichment analyses revealed that inflammation may be involved.  They were associated with correlative inflammation. Combined with PPI networks, these results revealed CytoHubba's top ten hub genes, including CCL2, CXCL12, CXCL1, CTGF/CCN2, CX3CR1, POSTN, FKBP5, SELE, AIF1and BMP2. Among them, CCL2, CXCL12, FKBP5 and BMP2 might be considered as prognostic and diagnostic biomarkers after LVAD support and have confirmed their validity in clinical datasets. The area under the curve of the four main hub genes was over 0.85, indicating high diagnostic ability and good prognosis for patients with DCM with LVAD implantation. However, A significant effect of CCL2, CXCL12, FKBP5 and BMP2 expression was not observed on left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), cardiac index (CI) or support-time of LVAD.
Conclusions CCL2, CXCL12, FKBP5 and BMP2 could be potential gene biomarkers for patients with DCM after LVAD support. These findings provide critical clues for the therapeutic management of patients with DCM and LVADs. LVEDD, LVEF, CI, and support-time LVAD were not correlated with expression of these hub genes.