Identification Of Key Genes In Calcific Aortic Valve By Bioinformatics Analysis

Background: Calcific aortic valve disease(CAVD)is very common in the elderly in china,and there is no effective drug treatment at present.A lot of research has been conducted,but the underlying molecular mechanism of CAVD is still unclear.Therefore,it is of great value to identify the significantly differentially expressed genes involved in the progression of CAVD and use them as new biomarkers or potential therapeutic targets for CAVD.Objective: The aim was to identify the key genes and pathways of CAVD by bioinformatics analysis.Methods: Gene expression profiles of GSE51472(including 5 normal aortic valves and 5 calcified aortic valves)were downloaded from the GEO database.The LIMMA software package in R software was used to screen the differentially expressed genes of CAVD.Functional and pathway enrichment analysis was conducted based on GO and KEGG pathway database information of different genes.Then,the STRING database,CYTOSCAPE software and MCODE plug-in were used to construct the protein-protein interaction(PPI)network and screen out the key genes.Results: A total of 772 differentially expressed genes(486 up-regulated genes and286 down-regulated genes)were identified,The main enriched biological processes include inflammation,immune response,chemokine signal transduction,and extracellular matrix metabolism.Through the MCODE plug-in unit,four up-regulated gene clustering modules and one down-regulated gene clustering module in the differentially expressed gene PPI network were identified.Among them,the main gene enrichment pathways include cytokine-receptor interactions and chemokine signaling pathways.The main gene enrichment pathways include cytokine-receptor interaction,chemokine signaling pathway,Staphylococcus aureus infection,hematopoietic cell lineage,tuberculosis,rheumatoid arthritis,osteoclast differentiation,NF-k B signaling pathway,and Toll-like receptor signaling pathway.Conclusion: This study found that 149 key up-regulated genes and 9 key down-regulated genes are significantly expressed in calcified aortic valve disease,among which some genes(such as IL6,SPP1,CCR2,MMP9,and VCAM1)have been shown to regulate calcified aortic valve disease.This study describes the biological processes,molecular functions and signal pathways involved in the significantly differentially expressed key genes in calcified aortic valves.It is helpful to understand the molecular mechanism of CAVD in the clinical work.The results of this study provide a feasible theoretical basis for later basic research,explore possible research directions in the future,such as apoptosis-related genes GZMA,GZMB;inflammation-infiltration-related genes IL6,CXCL8;immune response-related genes CD86,CD28;The extracellular matrix-related genes MMP9 and VCAM1 may be reliable biological targets for the diagnosis,treatment or delay of calcific aortic valve disease.