Identification of potential biomarkers and candidate smallmolecule drugs for heart failure via comprehensive gene microarray analysis

Abstract

Purpose: To identify potential novel biomarkers and to explore new small-molecule drugs for heart failure (HF). Methods: The Gene Expression Omnibus (GEO) microarray datasets were downloaded for analyzing the differentially expressed genes  (DEGs). Venn analysis was performed to calculate the overlapping genes which were then used for Gene Ontology (GO) analysis, and  Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using cluster Profiler in R package; a protein-protein interaction network (PPI) was constructed using STRING database. The hub genes were selected for small-molecule drug identification, while molecular  docking of small-molecule drugs and hub genes was performed using CBdock2. Results: Upregulated and downregulated DEGs were  obtained from GSE84796, GSE107569 and GSE116250 datasets, respectively. Eleven (11) overlapping genes, which were enriched in  collagen fiber tissue, collagen-containing extracellular matrix and collagen fiber-related pathways, were also enriched in AGE-RAGE and  relaxin signaling pathways. The PPI network of the DEGs was constructed, and five hub genes, with high connectivity, were significantly  upregulated in HF. The five hub genes were ranked as MFAP4, LTBP2, THBS4, COL3A1 and COL1A1. Two targets (COL1A1 and COL3A1) matched potential drugs, and fostamatinib shared by the two targets had the greatest therapeutic value for HF. Conclusion: Five novel  biomarkers and involved signaling pathways have been identified in HF via comprehensive microarray analyses. The results also show  that fostamatinib might be a promising drug candidate for HF treatment