Integrated identification of key immune related genes and patterns of immune infiltration in calcified aortic valvular disease: A network based meta-analysis

Abstract

Background: As the most prevalent valvular heart disease, calcific aortic valve disease (CAVD) has become a primary cause of aortic valve stenosis and insufficiency. We aim to illustrate the roles of immune related genes (IRGs) and immune cells infiltration in the occurrence of CAVD.Methods: Integrative meta-analysis of expression data (INMEX) was adopted to incorporate multiple gene expression datasets of CAVD from Gene Expression Omnibus (GEO) database. By matching the differentially expressed genes (DEGs) to IRGs from “ImmPort” database, differentially expressed immune related genes (DEIRGs) were screened out. We performed enrichment analysis and found that DEIRGs in CAVD were closely related to inflammatory response and immune cells infiltration. We also constructed protein–protein interaction (PPI) network of DEIRGs and identified 5 key DEIRGs in CAVD according to the mixed character calculation results. Moreover, CIBERSORT algorithm was used to explore the profile of infiltrating immune cells in CAVD. Based on Spearman’s rank correlation method, correlation analysis between key DEIRGs and infiltrating immune cells was performed.Results: A total of 220 DEIRGs were identified and the enrichment analysis of DEIRGs showed that they were significantly enriched in inflammatory responses. PPI network was constructed and PTPN11, GRB2, SYK, PTPN6 and SHC1 were identified as key DEIRGs. Compared with normal aortic valve tissue samples, the proportion of neutrophils, T cells CD4 memory activated and macrophages M0 was elevated in calcified aortic valves tissue samples, as well as reduced infiltration of macrophages M2 and NK cells activated. Furthermore, key DEIRGs identified in the present study, including PTPN11, GRB2, PTPN6, SYK, and SHC1, were all significantly correlated with infiltration of various immune cells.Conclusion: This meta-analysis suggested that PTPN11, GRB2, PTPN6, SYK, and SHC1 might be key DEIRGs associated with immune cells infiltration, which play a pivotal role in pathogenesis of CAVD.

Transcriptomic Analyses and Experimental Validation Identified Immune-Related lncRNA–mRNA Pair MIR210HG–BPIFC Regulating the Progression of Hypertrophic Cardiomyopathy

“…CIBERSORTx is a powerful tool that provides a detailed description of tissue composition using RNA-Seq data and is commonly used for immune cell infiltration analysis [ 16 , 17 ]. To examine the composition of immune cells in HCM and explore the association between immune cell composition and the online CIBERSORTx website, we used the reference expression matrix (LM22) generated from scRNA-Seq of 22 immune-cell types isolated from peripheral blood to calculate the proportions of each immune-cell type in the GSE180313 dataset ( Figure 6 A).…”

“…CIBERSORTx is a powerful tool that provides a detailed description of tissue composition using RNA-Seq data and is commonly used for immune cell infiltration analysis [16,17].…”

Identification of pyroptosis-associated genes with diagnostic value in calcific aortic valve disease

“…Based on previous studies, we constructed an easy-to-use website ( https://cavddiagnosis.shinyapps.io/EDstr/ ) for CAVD diagnosis. More datasets were included in our study compared to previous research on CAVD diagnosis models ( 14 , 60 ). Besides, the AUC values of ROC in the training group and two validation groups were all over 0.9.…”

Preliminary study on molecular mechanism of COVID-19 intervention by Polygonum cuspidatum through computer bioinformatics

“…The String database ( https://string-db.org/ ) is one of the most data-rich and widely used databases for studying protein interactions. [ 22 , 23 ] The String database has now been updated to Version 11.5. It contains information on over 14,000 species, over 60 million proteins and more than 20 billion interactions.…”