CD36 identified by weighted gene co-expression network analysis as a hub candidate gene in lupus nephritis
1Department of Nephrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
Insights
This study identified CD36 as a key gene in lupus nephritis (LN) pathogenesis using bioinformatics. CD36 may serve as a novel biomarker or therapeutic target for this severe kidney disease.
Area of Science:
- Nephrology
- Immunology
- Bioinformatics
Background:
- Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), often leading to end-stage renal disease.
- Current therapies for LN are limited, highlighting the urgent need to understand its molecular mechanisms.
- Bioinformatics approaches are valuable for identifying disease-related genes.
Purpose of the Study:
- To identify hub genes involved in the pathogenesis of lupus nephritis (LN) using weighted gene co-expression network analysis (WGCNA).
- To explore potential novel biomarkers or therapeutic targets for LN.
Main Methods:
- WGCNA was performed on the GSE104948 microarray dataset from the Gene Expression Omnibus (GEO) database, comparing 18 normal and 21 LN glomerular samples.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the identified LN-related module.
- Hub genes were screened using Maximal Clique Centrality (MCC) in sub-networks, with subsequent validation across multiple datasets and correlation with LN classification.
Main Results:
- A significant LN-related co-expression module was identified, enriched for inflammation, immune response, cytokine, and immune cell activation pathways.
- The gene CD36 was identified as a crucial hub candidate gene in LN pathogenesis.
- CD36 expression was validated as differentially expressed in LN across multiple datasets and correlated with WHO Lupus Nephritis Class.
Conclusions:
- CD36 is proposed as a novel and vital candidate gene in the pathogenesis of lupus nephritis (LN).
- CD36 holds potential as a future biomarker or therapeutic target for LN.
Abstract:
Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), which often progresses to end-stage renal disease (ESRD) and ultimately leads to death. At present, there are no definitive therapies towards LN, so that illuminating the molecular mechanism behind the disease has become an urgent task for researchers. Bioinformatics has become a widely utilized method for exploring genes related to disease. This study set out to conduct weighted gene co-expression network analysis (WGCNA) and screen the hub gene of LN. We performed WGCNA on the microarray expression profile dataset of GSE104948 from the Gene Expression Omnibus (GEO) database with 18 normal and 21 LN samples of glomerulus. A total of 5,942 genes were divided into 5 co-expression modules, one of which was significantly correlated to LN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the LN-related module, and the module was proved to be associated mainly with the activation of inflammation, immune response, cytokines, and immune cells. Genes in the most significant GO terms were extracted for sub-networks of WGNCA. We evaluated the centrality of genes in the sub-networks by Maximal Clique Centrality (MCC) method and CD36 was ultimately screened out as a hub candidate gene of the pathogenesis of LN. The result was verified by its differentially expressed level between normal and LN in GSE104948 and the other three multi-microarray datasets of GEO. Moreover, we further demonstrated that the expression level of CD36 is related to the WHO Lupus Nephritis Class of LN patients with the help of Nephroseq database. The current study proposed CD36 as a vital candidate gene in LN for the first time and CD36 may perform as a brand-new biomarker or therapeutic target of LN in the future.
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