A Comprehensive Study on Molecular Characteristics and Clinical Prognosis of Immune- Related Genes in Idiopathic Pulmonary Fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease with unclear pathogenesis. Immune-related genes (IRGs) are increasingly recognized as key players in its development, but their prognostic value remains underexplored. Methods: Using the GSE70866 dataset, we identified differentially expressed IRGs (DE-IRGs) by intersecting IRGs (from ImmPort) with differentially expressed genes. Prognostic IRGs were refined via univariate Cox, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression, yielding four independent factors (PPBP, CCL7, ADM, SFTPD) to construct a risk model. The model was validated in training and validation cohorts, with immune infiltration analyzed via Single-sample gene set enrichment analysis (ssGSEA). In vitro and in vivo experiments verified gene expression, particularly PPBP’s role in fibrosis. Conclusions: The IRG-based risk model effectively stratified IPF prognosis. PPBP was abnormally elevated in IPF, and its knockdown inhibited fibroblast activation and fibrosis progression. These findings highlight PPBP as a critical pathogenic factor, offering novel prognostic and therapeutic insights for IPF.