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.