Molecular Mechanisms Underlying the Progression of Aortic Valve Stenosis: Bioinformatic Analysis of Signal Pathways and Hub Genes

Figures

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  Figure 1. Gene expression and UMAP for each sample: (A) Gene expression data from GSE83453 and GSE51472, with the sample list on the horizontal axis and the log2-converted gene expression values on the vertical axis. Green bars represent tissue samples from patients with aortic stenosis, and purple bars represent control samples. (B) UMAP analysis was performed on each sample from the GSE83453 and GSE51472 datasets. Data from aortic stenosis and control subjects were relatively distinct, with green dots representing tissue samples from patients with aortic stenosis and purple dots representing control samples. UMAP, uniform manifold approximation and projection.

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  Figure 2. Volcano plots, cluster heatmaps, and DEG Venn diagrams for the GSE83453 and GSE51427 datasets: (A) Volcano plots for the GSE83453 (left panel) and GSE51427 (right panel) datasets. Red dots represent upregulated genes based on an adjusted p-value < 0.05 and log2FC ≥ 1. Blue dots represent downregulated genes based on an adjusted p-value < 0.05 and log2FC ≥ −1. Black dots represent genes with no significant difference. (B) Cluster heatmap of the top 20 significant genes of the GSE83453 (left) and GSE51427 (right) datasets. Yellow indicates upregulated gene expression, blue indicates downregulated gene expression, and green indicates no significant change in gene expression. (C) Venn diagram of DEGs in the highly expressed upregulated or downregulated top 300 genes in each dataset (GSE83453 and GSE51427): (left panel) five overlapping DEGs upregulated in the two datasets; (right panel) eight overlapping DEGs downregulated in the two datasets. GSE83453 had 258 DEGs, comprising 138 upregulated and 120 downregulated genes, while GSE51427 included 236 DEGs, comprising 113 upregulated and 123 downregulated genes. DEG, differentially expressed gene; AS, aortic valve stenosis; log2FC; log2…

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  Figure 3. Differential gene expression analysis and functional enrichment analysis of DEGs using Metascape: (A) Venn diagram plot of differential gene expression analysis using GEOexplorer. A total of 10,875 genes were identified from a combined dataset of GSE83453 and GSE51472. Among these genes, 4361 genes were identified as common DEGs. (B) Heatmap plot generated by GEOexplorer using the combined GSE83453 and GSE51472 dataset. The top 20 most significant genes were analyzed. (C) Bar graph of enriched terms across the top 100 genes list from the GSE83453 and GSE51472 datasets, colored according to p-values. (D) Network of the top 20 clusters of enriched terms in Metascape. Cluster identification is represented by color, and the similarity score is represented by the thickness of the edge. DEGs, differentially expressed genes.

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  Figure 4. PPI network analysis of DEGs in patients with aortic sclerosis datasets (GSE83453 and GSE51472). The 3D-PPI network analysis was performed using NetworkAnalyst, with DEGs highlighted in orange. The top 10 hub genes with the highest number of connections are listed (Table 4). PPIs, protein–protein interactions; DEGs, differently expressed genes; VCAM1, vascular cell adhesion molecule 1; FHL2, four-and-a-half LIM domain protein 2; RUNX1, runt-related transcription factor 1; TNFSF10, TNF superfamily member 10; PLAU, plasminogen activator, urokinase receptor; SPOCK1, sparc/osteonectin, cwcv, and kazal-like domains proteoglycan (testican) 1; CD74, cluster of differentiation 74; SIPA1L2, signal-induced proliferation-associated 1 like 2; TRIB1, Tribbles pseudokinase 1; CXCL12, C-X-C motif chemokine ligand 12; YWHA, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta; PARP1, poly(ADR-Ribose) polymerase 1; TJP, tight junction protein; IRS2, insulin receptor substrate; BMX, BMX non-receptor tyrosine kinase; SOCS2, suppressor of cytokine signaling 2; PRDX6, peroxiredoxin 6; ARID3A, AT-rich interaction domain 3; TSHZ3, teashirt zinc finger homeobox 3; RGS16, regulator…