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Identification of differentially expressed genes and pathways in kidney of ANCA-associated vasculitis by integrated
Xu Deng1, Junying Gao2, Fei Zhao1
1Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, P. R. China.
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.
Insights
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) involves the kidneys. This study identified key genes and pathways, like complement and coagulation cascades, crucial for AAV kidney disease development and potential therapeutic targets.
Area of Science:
- Nephrology
- Immunology
- Genomics
Background:
- Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare autoimmune disease.
- Kidney involvement is a common and critical manifestation of AAV, impacting prognosis.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) and key pathways in kidney tissue of AAV patients.
- To uncover potential biomarkers and therapeutic targets for AAV kidney disease.
Main Methods:
- Integrated multiple gene expression datasets (GSE104948, GSE104954, GSE108109, GSE108112, GSE108113) from the Gene Expression Omnibus (GEO) database using the Robust Rank Aggregation (RRA) method.
- Performed Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) network analysis using Cytoscape.
- Identified hub genes (ALB, TYROBP, CYBB) and validated key pathways in both glomerular and tubulointerstitial compartments.
Main Results:
- Identified DEGs in kidney tissue between AAV patients and healthy controls.
- GO analysis indicated the involvement of immunity and metabolism in AAV kidney disease.
- KEGG analysis highlighted the crucial roles of complement and coagulation cascades, *Staphylococcus aureus* infection, COVID-19, and systemic lupus erythematosus (SLE) pathways.
- ALB, TYROBP, and CYBB were identified as significant hub genes present in both glomerular and tubulointerstitial datasets.
Conclusions:
- This study elucidates key genes and pathways implicated in kidney damage in AAV.
- Findings provide a foundation for understanding AAV pathogenesis, developing diagnostic biomarkers, and exploring novel therapeutic strategies.
