Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Identification of potential biomarkers and candidate small-molecule drugs for heart failure via comprehensive gene microarray analysis

Hailang Liu, Chunyang Yu, Zhongcheng Wei, Qing Zhang

Department of Cardiology, The Affiliated Huai'an No.1 People’s Hospital of Nanjing Medical University, Huai'an City, Jiangsu Province 223300, China;

For correspondence:- Qing Zhang Email: lhl2ny@yeah.net Tel:+8651780872604

Accepted: 2 October 2023 Published: 30 October 2023

Citation: Liu H, Yu C, Wei Z, Zhang Q. Identification of potential biomarkers and candidate small-molecule drugs for heart failure via comprehensive gene microarray analysis. Trop J Pharm Res 2023; 22(10):2067-2073 doi: 10.4314/tjpr.v22i10.7

© 2023 The authors.
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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 CB-dock2.

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.

Keywords: Bioinformatics analysis, Biomarker, Candidate small-molecules, Fostamatinib, Heart failure