Ankylosing spondylitis (AS) is a disabling chronic inflammatory disease. Mechanisms of ferroptosis in AS remain unclear. Using bioinformatics analysis, we aimed to identify key molecules involved in ferroptosis, provide potential therapeutic targets for AS, and further explore mechanisms of ferroptosis in AS.

GSE25101 was downloaded from the Gene Expression Omnibus and intersected with a ferroptosis gene dataset. The ferroptosis‐relate differentially‐expressed genes were further subjected to functional enrichment analysis, protein interaction network analysis, and gene‐miRNA interaction network analysis, from which potential key ferroptosis genes in the pathogenesis of ankylosing spondylitis were screened.

A total of 20 differentially expressed genes were screened, most of which are involved in phosphoinositide 3 kinase‐Akt or mitogen‐activated protein kinase (MAPK) signaling pathways or the endoplasmic reticulum stress response. The following target genes were identified through protein‐protein interaction network analysis and screening of key modules constructed from genes associated with PI3K‐Akt and MAPK signaling pathways: TP53, PTEN, TLR4, HSPB1, DDIT3, and XBP1. In addition, PI3K‐Akt and MAPK signaling were associated with oxidative stress, which may play a role in AS pathological ossification related to ferroptosis. Only hsa‐miR‐205‐5p was found to target at least two genes by gene‐miRNA interaction network analysis.

Future therapeutic drug development may intervene by modulating MAPK or PI3K‐Akt signaling pathways rather than directly affecting the interleukin 17 pathway. hsa‐miR‐205‐5p may be a potential novel biomarker for AS.