Identification of differentially expressed genes and pathways in kidney of ANCA-associated vasculitis by integrated bioinformatics analysis

Abstract

The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systematic of relatively rare autoimmune diseases with unknown cause. Kidney involvement is one of the most common clinical manifestations, and the degree of renal damage is closely associated with the development and prognosis of AAV. In this study, we utilized the Robust Rank Aggreg (RRA) method in R to integrate GSE104948, GSE104954, GSE108109, GSE108112, and GSE108113 profile datasets loaded from Gene Expression Omnibus (GEO) database and identified a set of differentially expressed genes (DEGs) in kidney between AAV patients and living donors. Then, the results of gene ontology (GO) functional annotation showed that immunity and metabolism involved process of AAV both in glomerulus and tubulointerstitial. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that following pathways, such as complement and coagulation cascades pathway; Staphylococcus aureus infection; disease-COVID-19; and systemic lupus erythematosus (SLE) pathway play a crucial role in AAV. Next, the results analyzed by protein-protein interaction (PPI) network and Cytoscape software exhibited the hub genes ALB, TYROBP, and CYBB existed in both glomerular and tubulointerstitial compartments datasets. Finally, KEGG analysis using genes of two most important modules also further validated complement and coagulation cascades pathway and S. aureus infection existed both in glomerulus and tubulointerstitial compartments datasets. In conclusion, this study identified key genes and pathways involved in kidney of AAV, which was benefit to further uncover the mechanisms underlying the development and progress of AAV, biomarkers, and potential therapeutic targets as well.

Keywords: Antineutrophil cytoplasmic antibody-associated vasculitis; Gene Expression Omnibus database; differentially expressed genes; integrated bioinformatics analysis; kidney.

Figure 1.

Differentially expressed genes between the two groups of samples in each dataset (A) GSE104948, (B) GSE104954, (C) GSE108109, (D) GSE108112. The red dots represent the upregulated genes based on an adjusted p < 0.05 and |log fold change| > 1; the blue dots represent the downregulated genes based on an adjusted p < 0.05 and |log fold change| > 1; the black spots represent genes with no significant difference in expression.

Figure 2.

Cluster heatmap of the top 75 DEGs (A) GSE104948, (B) GSE104954, (C) GSE108109, (D) GSE108112.

Figure 3.

LogFC heatmap of integrated datasets (A) Glomerular compartments DEGs, (B) Tubulointerstitial compartments DEGs, (C) Glomerular and tubulointerstitial compartments DEGs. The abscissa represents the GEO IDs, the ordinate represents the gene name, the red represents logFC > 0, the green represents logFC < 0 and the value in the box represents the logFC value.

Figure 4.

Integrated DEGs in kidney of AAV for enriched GO terms (A) Glomerular compartments DEGs, (B) Tubulointerstitial compartments DEGs, (C) Glomerular and tubulointerstitial compartments DEGs. BP: biological process, CC: cell component, MF: molecular function.

Figure 5.

KEGG pathway enrichment analysis of the integrated DEGs (A) Glomerular compartments DEGs, (B) Tubulointerstitial compartments DEGs, (C) Glomerular and tubulointerstitial compartments DEGs. The red bars represent top 15 pathways from upregulated DEGs in each integrated dataset. The blue bars represent top 15 pathways from downregulated DEGs in each integrated dataset.

Figure 6.

PPI network of different expression genes (A) Glomerular compartments DEGs, (B) Tubulointerstitial compartments DEGs, (C) Glomerular and tubulointerstitial compartments DEGs.

Figure 7.

Hub genes of different expression genes (A, D) Glomerular compartments DEGs, (B, E) Tubulointerstitial compartments DEGs, (C, F) Glomerular and tubulointerstitial compartments DEGs. The dark of yellow is positively associated with the degree values.

Figure 8.

The module1 and module2 of different expression genes (A, B) Module1 and module2 in glomerular compartments DEGs, (C, D) Module1 and module2 in tubulointerstitial compartments DEGs, (E, F) Module1 and module2 in glomerular and tubulointerstitial compartments DEGs. The genes involved in module1 or module2 labeled in yellow.