BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible, and fatal disease characterized by progressive interstitial lung fibrosis. Given its insidious onset and poor outcome, there is an urgent need to elucidate the molecular mechanisms underlying IPF and identify effective therapeutic targets and diagnosis and prognosis biomarkers. Ferroptosis is an iron-dependent form of programmed cell death that occurs as lipid peroxides accumulate. Growing evidence suggests that ferroptosis is important in IPF. METHODS: Human ferroptosis PCR array was performed on IPF and control lung tissue. The differentially expressed ferroptosis-related genes (DE-FRGs) were identified, underwent functional enrichment analyses, protein-protein interaction network construction, and potential drug target prediction. The DE-FRGs were validated and their value as diagnostic and prognostic blood biomarkers were evaluated using the Gene Expression Omnibus dataset GSE28042. RESULTS: The array identified 13 DE-FRGs. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the DE-FRGs were mainly related to iron ion transport, blood microparticles, and oxidoreductase activity, and were involved in porphyrin metabolism, necroptosis, and the p53 signaling pathway in addition to ferroptosis. The 13 DE-FRGs were analyzed using the Drug-Gene Interaction Database to explore novel IPF therapeutic agents, yielding 42 potential drugs. Four DE-FRGs (BBC3, STEAP3, EPRS, SLC39A8) in the peripheral blood of IPF patients from the GSE28042 dataset demonstrated the same expression pattern as that observed in the lung tissue array. The receiver operating characteristic analysis demonstrated that the area under the curve of STEAP3 and EPRS were >
0.75. The survival analysis demonstrated that STEAP3 and EPRS were significantly different between the IPF and control groups. CONCLUSIONS: The FRG expression profiles in IPF and control lung tissue were characterized. The findings provided valuable ideas to elucidate the role of ferroptosis in IPF and aided the identification of novel IPF therapeutic targets and biomarkers.