Mining of Potential Biomarkers and Pathway in Valvular Atrial Fibrillation (VAF) via Systematic Screening of Gene Coexpression Network

PURPOSE: We apply the bioinformatics method to excavate the potential genes and therapeutic targets associated with valvular atrial fibrillation (VAF). METHODS: The downloaded gene expression files from the gene expression omnibus (GEO) included patients with primary severe mitral regurgitation complicated with sinus or atrial fibrillation rhythm. Subsequently, the differential gene expression in left and right atrium was analyzed by R software. Additionally, weighted correlation network analysis (WGCNA), principal component analysis (PCA), and linear model for microarray data (LIMMA) algorithm were used to determine hub genes. Then, Metascape database, DAVID database, and STRING database were used to annotate and visualize the gene ontology (GO) analysis, KEGG pathway enrichment analysis, and PPI network analysis of differentially expressed genes (DEGs). Finally, the TFs and miRNAs were predicted by using online tools, such as PASTAA and miRDB. RESULTS: 20,484 differentially expressed genes related to atrial fibrillation were obtained through the analysis of left and right atrial tissue samples of GSE115574 gene chip, and 1,009 were with statistical significance, including 45 upregulated genes and 964 downregulated genes. And the hub genes implicated in AF of NPC2, ODC1, SNAP29, LAPTM5, ST8SIA5, and FCGR3B were screened. Finally, the main regulators of targeted candidate biomarkers and microRNAs, EIF5A2, HIF1A, ZIC2, ELF1, and STAT2, were found in this study. CONCLUSION: These hub genes, NPC2, ODC1, SNAP29, LAPTM5, ST8SIA5, and FCGR3B, are important for the development of VAF, and their enrichment pathways and TFs elucidate the involved molecular mechanisms and assist in the validation of drug targets.