Integrated bioinformatic analysis reveals immune molecular markers and potential drugs for diabetic cardiomyopathy

Figures

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  Figure 1. Study workflow. DCM, Diabetic cardiomyopathy; GEO, Gene Expression Omnibus; GO, Gene Ontology; PPI, protein-protein interaction; cMAP, Connectivity Map; KEGG, Kyoto Encyclopedia of Genes and Genomes; GSEA, Gene Set Enrichment Analysis; TF, transcription factors; DEGs, differentially expressed genes; WGCNA, Weight gene co-expression network analysis; GEPIA, Gene Expression Profiling Interactive Analysis; QPCR, quantitative real-time PCR; WB, Western blotting.

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  Figure 2. Gene co-expression modules. (A) Analysis of network topology for soft-thresholding powers. (B) Hierarchical cluster dendrogram of DCM-related genes based on one dissimilarity measure. (C) Module-phenotype associations.

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  Figure 3. Immune infiltration analysis and intersection dataset. (A) Boxplot diagram of proportions of 22 types of immune cells. (B) Venn diagram of intersection of black modules and immune genes. * means p value <0.05; ** means p value <0.01; *** means p value <0.001.

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  Figure 4. Density plots of the dataset GSE4745, showing a smooth distribution of the points along the numeric axis. The peaks of the density plot are at the locations with the highest concentration of points. (A) density plot of sample dataset. (B–F) Density plots of hub genes.

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  Figure 5. DCM-related gene set enrichment analysis. (A) Cell component. (B) Molecular function. (C) KEGG pathway. (D) Reactome.

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  Figure 6. Gene expression and validation. (A) Dataset gene expression; (B) Murine DCM gene expression; (C) ROC for gene expression in dataset; (D) ROC curve for murine DCM gene expression.

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  Figure 7. Binding sites of transcription factors and expression correlation verification. (A) Binding site of Prdm5; (B) Binding site of Gata4; (C) Binding site of Klf4; (D) Correlation between Prdm5 and Edn1 gene expression in myocardial tissue; (E) Correlation between Gata4 and Edn1 gene expression in myocardial tissue; (F) Correlation between Klf4 and Edn1 gene expression in myocardial tissue.

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  Figure 8. Protein level expression of hub genes. Ns means p value >0.05;* means p value <0.05; ** means p value <0.01; *** means p value <0.001.

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  Figure 9. Molecular docking simulations. (A) EDN1 with telomerase inhibitor IX. (B) EDN1 with isoliquiritigenin. (C) EDN1 with medrysone. (D) EDN1 with benzoic acid. (E) EDN1 with oxymetholone. (F) EDN1 with sulforaphane. (G) EDN1 with epoxycholesterol. (H) 2-chloro-6-(1-piperazinyl)pyrazine.

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  Figure 10. ROC curves of the virtual filter for (A) isoliquiritigenin; (B) medrysone; (C) benzoic acid; (D) oxymetholone; (E) sulforaphane; (F) pevonedistat; (G) 2-chloro-6-(1-piperazinyl)pyrazine.