Autophagy-Related Genes Associated with Immune Cell Infiltration in Rheumatoid Arthritis Identified by Integrated Weighted Gene Co-Expression Network

Abstract

Background: Despite the evidence showing deregulation of autophagy to play a part in the pathogeneis of rheumatoid arthritis (RA), its role in the etiology of RA remains largely unknown. The aim of this study was to identify novel differentially expressed autophagy-related genes (DEARGs) in RA and their role in its pathogenesis. Methods: DEARGs and central modules of RA were obtained, using weighted gene co-expression network analysis (WGCNA) from GSE55457 dataset of the Gene Expression Omnibus database. Enrichment analysis was used for the identification of potential functions and pathways of the hub modules. Hub genes were obtained via intersection of DEARGs and turquoise modules, and their expressions were verified using GSE55235 and GSE97779 datasets and quantitative real-time polymerase chain reaction (qRT-PCR). CIBERSORT was used to assess single cell infiltration of RA and to assess the relevance of hub genes to immune cells. Results: A total of 14 DEARGs were obtained. Enrichment analysis showed hub modules and genes to be associated with immune and inflammatory related pathways. CC chemokine receptor 2 (CCR2+) and Caspase-1 (CASP1) were identified as potential biomarkers of RA. Furthermore, immune cell infiltration analysis showed that CCR2+ and CASP1 to be associated with T cell CD8+ and activated NK cells, among others. Conclusions: CCR2+ and CASP1 may be involved in RA development, via immune homeostasis, and may serve as potential markers for RA diagnosis and treatment. These findings may provide therapeutic targets for immune-based therapies and expand the understanding of RA etiology.