Abstract
BACKGROUND The aim of this study was to identify feature autophagy-related genes (ARGs) in systemic lupus erythematosus (SLE), evaluate their diagnostic value, and further explore DNA methylation and expression levels in the pathogenesis of SLE. MATERIAL AND METHODS WGCNA was used to construct network and selected hub genes based on gene expression dataset GSE81622. ARGS were overlapped with hub genes, and feature ARGs were identified. A diagnostic model was established by these feature ARGs using LASSO. GSE96879 was used to analyze the methylation levels of feature ARGs. The expression and methylation levels of feature ARGs were verified using RT-PCR and methylation-specific PCR. RESULTS We found that 55 hub genes were highly connected to the red module of WGCNA, and ARGs were extracted from the Human Autophagy Database and the GO_AUTOPHAGY gene set. Overlapping of 55 hub gene with ARGs resulted in 18 feature ARGs. S100A8, MyD88, and NCR3 from the 18 feature ARGs showed higher good diagnostic value for SLE. Five differentially methylated positions locating to S100A8, MyD88, and NCR3 genes were identified from GSE96879. After validation tests, RT-PCR showed that gene expressions of MyD88 and S100A8 were increased in the PBMCs samples of SLE patients compared with healthy controls, whereas NCR3 was the opposite. MSP found that cg24898863 (S100A8) was hypomethylated, while cg27490128 (NCR3) was hypermethylated in the SLE group, and S100A8 and NCR3 methylation were positively correlated with their expressions. CONCLUSIONS Our present study identified the potential roles of feature ARGs in SLE diagnosis, and shows correlation among DNA methylation and gene expressions of these feature ARGs in SLE.