Integrative multi-omics and experimental validation identify SERINC2 as a ferroptosis-related biomarker in idiopathic pulmonary fibrosis

Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited therapeutic options. Ferroptosis, an iron-dependent cell death, has been implicated in various fibrotic diseases, but its role in IPF remains unclear. This study integrates spatial transcriptomics, single-cell RNA sequencing, and bulk RNA-seq to explore ferroptosis in IPF. A ferroptosis scoring model and machine learning algorithms identified SERINC2 as a key gene upregulated across all datasets, with high expression in basal cells. Further analysis revealed that SERINC2⁺ basal cells are involved in key signaling pathways, such as Wnt and NT, and exhibit active intercellular communication. Animal experiments confirmed that SERINC2 protein levels are elevated in the lung tissues of BLM-induced mice, supporting its role in disease progression. Our findings suggest that SERINC2 may serve as a potential diagnostic biomarker and therapeutic target, providing new insights into the pathogenesis and potential treatment of IPF.