Identification of potential ferroptosis key genes and immune infiltration in rheumatoid arthritis by integrated bioinformatics analysis.

OBJECTIVE

Ferroptosis is of vital importance in the development of Rheumatoid arthritis (RA). The purpose of this project is to clarify the potential ferroptosis-related genes, pathways, and immune infiltration in RA by bioinformatics analysis.

METHODS

We acquired ferroptosis-related genes (FRGs) from Ferroptosis database (FerrDb). We obtained the Gene dataset of RA (GSE55235) from the Gene Expression Omnibus (GEO) Database, screened the differentially expressed genes (DEGs) in RA and control samples, and then took the intersection of it and FRGs. Aiming to construct the protein-protein interaction (PPI) networks of the FRGs-DEGs, STRING database and Cytoscape software 3.7.0 would be used. Furthermore, hub genes were identified by CytoNCA, a Cytoscape plug-in. The gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of FRGs-DEGs were performed.

RESULTS

We identified 34 FRGs-DEGs, including 7 upregulated and 27 downregulated genes by taking the intersection of the FRGs and DEGs. PPI analysis identified a total of 3 hub genes(VEGFA, PTGS2, and JUN). GO enrichment analyses and KEGG Pathway enrichment displayed that the FRGs-DEGs are involved in the response to oxidative stress and corticosteroid, heme binding, FoxO-signal pathway. Results of immune infiltration displayed that increased infiltration of T cells, while Macrophages M2 less may be related to the occurrence of RA.

CONCLUSION

The hub genes involved in ferroptosis in RA may be VEGFA, PTGS2, and JUN, which are mainly involved in FoxO-signal pathway. T cell, Mac, and plasma cells may be involved in the regulation of RA-joints-synovial-inflammation.