Identification of potential biomarkers in Rheumatoid Arthritis based on DNA methylation and scRNA-Seq

Introduction: Rheumatoid arthritis (RA) is a chronic, symmetrical, chronic autoimmune disease marked by symmetric joint inflammation. Its high rate of disability has severe implications for society and individuals. Therefore, effective and reliable diagnostic markers and therapeutic targets are required for RA. Methods: 657 differentially expressed genes (DEGs) in CD16+ monocyte clusters were identified according to proportion and immune score. The interaction intensity of CD8+T cell clusters in RA was elevated, with strong interaction. The output signals of platelets, monocytes, and NK cells in RA were higher, as were the incoming signals of CD8+T cells. According to the incoming and outgoing cells, 10 ligand-receptor pairs were highly expressed in RA. Then, the association analysis of DEGs and differentially methylated genes (DMGs) was conducted by limma and methylKit, and four key genes were found. The expression analysis of these four genes in the validation set, ROC curves of the training and validation sets, and gene correlation analysis were conducted, respectively. Results: Four key genes of IFI44L (cg05696877), ISG15 (cg20062691), TAP1 (cg16853860), and TNFSF10 (cg01059398) were found. The immune gene TNFSF10 had an AUC value > 0.9 in both the training and validation sets, indicating significant diagnostic ability. Discussion: TNFSF10 had good diagnostic performance in RA, experiments or potential clinical assays were required to validate it Conclusion: The TNFSF10 expression correlates with multiple tumor types and the degree of immune cell invasion. Therefore, this gene may be a potential target for human diseases, such as RA and tumors. conclusion: Our study reveals a possible mechanism for TNFSF10 in RA pathogenesis and suggests that this gene may be a potential target for human diseases, such as RA and tumors.