Comparative Analysis on Abnormal Methylome of Differentially Expressed Genes and Disease Pathways in the Immune Cells of RA and SLE

Abstract

We identified abnormally methylated, differentially expressed genes (DEGs) and pathogenic mechanisms in different immune cells of RA and SLE by comprehensive bioinformatics analysis. Six microarray data sets of each immune cell (CD19+ B cells, CD4+ T cells and CD14+ monocytes) were integrated to screen DEGs and differentially methylated genes by using R package “limma.” Gene ontology annotations and KEGG analysis of aberrant methylome of DEGs were done using DAVID online database. Protein-protein interaction (PPI) network was generated to detect the hub genes and their methylation levels were compared using DiseaseMeth 2.0 database. Aberrantly methylated DEGs in CD19+ B cells (173 and 180), CD4+ T cells (184 and 417) and CD14+ monocytes (193 and 392) of RA and SLE patients were identified. We detected 30 hub genes in different immune cells of RA and SLE and confirmed their expression using FACS sorted immune cells by qPCR. Among them, 12 genes (BPTF, PHC2, JUN, KRAS, PTEN, FGFR2, ALB, SERB-1, SKP2, TUBA1A, IMP3, and SMAD4) of RA and 12 genes (OAS1, RSAD2, OASL, IFIT3, OAS2, IFIH1, CENPE, TOP2A, PBK, KIF11, IFIT1, and ISG15) of SLE are proposed as potential biomarker genes based on receiver operating curve analysis. Our study suggests that MAPK signaling pathway could potentially differentiate the mechanisms affecting T- and B- cells in RA, whereas PI3K pathway may be used for exploring common disease pathways between RA and SLE. Compared to individual data analyses, more dependable and precise filtering of results can be achieved by integrating several relevant data sets.

Identification and Validation of IFI44 as Key Biomarker in Lupus Nephritis

“…In addition, HERC5, RSAD2, and DDX60 are all interferon induced-genes, which play important roles in antiviral response ( 36 – 39 ). Consistent with our findings, recent studies revealed that the expression level of RSAD2 was markedly increased in the SLE samples compared with controls, which may act as a potential biomarker gene and therapeutic target for the treatment of SLE ( 40 , 41 ). Similarly, upregulated gene expression of DDX60 was observed in the IFN-I-positive childhood-onset SLE patients ( 42 ).…”

Tuning Monocytes and Macrophages for Personalized Therapy and Diagnostic Challenge in Rheumatoid Arthritis

“…Microarray data also identified 193 aberrantly methylated genes in RA monocytes. Further enrichment analysis demonstrated elevated methylation of SIRT1, SKP2, TUBA1A, IMP3, EXOSC5 and SMAD4 genes and reduced methylation of KRAS in samples from RA patients compared to healthy individuals [43]. In addition, hypomethylation of the CYP2E1 and DUSP22 promoters in RA monocytes correlates with RA activity [44].…”

miR‑425 regulates lipophagy via SIRT1 to promote sorafenib resistance in liver cancer

“…GSE93595 and GSE94550) ( 20 , 21 ) were obtained from . The gene expression matrix for the TCGA datasets was analyzed using R software v4.0.2 (limma package v3.44.3) ( 22 , 23 ) using log fold-change (FC) >0.6 or logFC <-0.6 and P<0.05 as the cut-off values, and the correlation between miR-425 and SIRT1 expression was evaluated using Pearson correlation analysis with SPSS (22.0; IBM, Corp.). GEO datasets were analyzed with GEO2R (v3.2.3) ( Table SI ) ( 24 , 25 ), and Venn diagrams were generated with VennDiagram (v1.2.20) ( 24 , 25 ).…”