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

Yihua Fan; Yuan Li; Xiaoyan Fu; Jing Peng; Yuchi Chen; Tao Chen; Di Zhang

doi:10.1016/j.heliyon.2023.e21167

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

Heliyon. 2023 Oct 18;9(11):e21167. doi: 10.1016/j.heliyon.2023.e21167. eCollection 2023 Nov.

Authors

Yihua Fan¹, Yuan Li¹, Xiaoyan Fu¹, Jing Peng¹, Yuchi Chen¹, Tao Chen¹, Di Zhang²

Affiliations

¹ Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China.
² Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong Province, China.

Abstract

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.

Keywords: Bioinformatics analysis; Ferroptosis; Gene expression omnibus; Immune infiltration; Rheumatoid arthritis.