Identification of key genes in calcific aortic valve disease via weighted gene co-expression network analysis

Jin-Yu Sun,Yue-Yun Shen,Jun-Yan Kan,Xiang-Qing Kong,Hui Shen,Wei Sun,Yang Hua,Qiang Qu

doi:10.1186/s12920-021-00989-w

Abstract

BackgroundCalcific aortic valve disease (CAVD) is the most common subclass of valve heart disease in the elderly population and a primary cause of aortic valve stenosis. However, the underlying mechanisms remain unclear.MethodsThe gene expression profiles of GSE83453, GSE51472, and GSE12644 were analyzed by ‘limma’ and ‘weighted gene co-expression network analysis (WGCNA)’ package in R to identify differentially expressed genes (DEGs) and key modules associated with CAVD, respectively. Then, enrichment analysis was performed based on Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, DisGeNET, and TRRUST database. Protein–protein interaction network was constructed using the overlapped genes of DEGs and key modules, and we identified the top 5 hub genes by mixed character calculation.ResultsWe identified the blue and yellow modules as the key modules. Enrichment analysis showed that leukocyte migration, extracellular matrix, and extracellular matrix structural constituent were significantly enriched. SPP1, TNC, SCG2, FAM20A, and CD52 were identified as hub genes, and their expression levels in calcified or normal aortic valve samples were illustrated, respectively.ConclusionsThis study suggested that SPP1, TNC, SCG2, FAM20A, and CD52 might be hub genes associated with CAVD. Further studies are required to elucidate the underlying mechanisms and provide potential therapeutic targets.

Highlights

Calcific aortic valve disease (CAVD) is the most common subclass of valve heart disease in the elderly population and a primary cause of aortic valve stenosis [1]
Our study identified Differentially expressed gene (DEG) between calcified and normal aortic valve samples based on the gene expression profiles of GSE83453 and GSE51472, GSE12644
DEGs between calcified and normal aortic valve After data pre-processing of the dataset GSE83453, GSE51472, and GSE1264, we screened DEGs according to the cut-off criterion of adjusted P-value < 0.05 and |log2 FC| ≥ 0.5

Summary

Introduction

Calcific aortic valve disease (CAVD) is the most common subclass of valve heart disease in the elderly population and a primary cause of aortic valve stenosis [1]. It was reported that the incidence of aortic valve stenosis was 2% in patients ≥ 65 years old, whereas aortic valve. In CAVD, the fibro-calcific remodeling and pathological thickening of the aortic valve disturb pressure overload and hemodynamic stability. Mechanisms underlying the development or progression of CAVD remain unclear, and there lacks conservative treatment against CAVD. Calcific aortic valve disease (CAVD) is the most common subclass of valve heart disease in the elderly population and a primary cause of aortic valve stenosis.

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Results

Discussion

Conclusion