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.
Highlights
Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease characterized by autoantibody production, complement activation and immune complex deposition
The correlation matrix was transformed to an adjacency matrix with an appropriate soft-thresholding value β
The association between CD36 and WHO Lupus Nephritis Class showed directly that the expression level of CD36 gradually up-regulates along with the development of Lupus nephritis (LN) evaluated by WHO Lupus Nephritis Class, providing strong evidence that the abnormal over-expression of CD36 is an important element in the pathogenesis of LN
Summary
Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease characterized by autoantibody production, complement activation and immune complex deposition. The incidence of SLE ranges from 0.03 to 2.32 person-years worldwide (Rees et al, 2017). Lupus nephritis (LN) is one of the most frequent and severe organ manifestations in patients with SLE, the hallmark of which is often glomerulonephritis. How to cite this article Yang H, Li H. CD36 identified by weighted gene co-expression network analysis as a hub candidate gene in lupus nephritis.
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