Bioinformatic analysis of senescence-related genes as potential biomarkers in idiopathic pulmonary fibrosis

Abstract The pathogenesis of Idiopathic pulmonary fibrosis (IPF) is unclear. Many studies have provided evidence of accelerated senescence in IPF pathogenesis. This study aimed to identify the cellular senescence-related genes (SRGs) as potential biomarkers for IPF diagnosis. Cellular SRGs were identified using the Gene Cards database. The GSE24206, GSE53845, and GSE68239 datasets for IPF patients and healthy controls were downloaded using the gene expression omnibus database. Differentially expressed genes (DEGs) in IPF were identified and analyzed using the gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analyses. Differentially expressed SRGs (DESRGs) were identified using the weighted gene co-expression network analysis R package and protein-protein interaction network. Hub genes among the DESRGs were screened using the receiver operating characteristic curves, and the expression of hub genes was validated in IPF and lung tissues of healthy donors using single-cell sequencing analysis. Finally, we screened three DESRGs: C‑X‑C motif chemokine ligand 12 (CXCL12), caveolin-1 (CAV1), and C-X-C motif chemokine receptor 2 (CXCR2). CXCL12 was highly expressed in the endothelial cells and downregulated in fibroblasts of IPF patients. CAV1 expression was upregulated in endothelial and mural cells and downregulated in epithelial cells of IPF patients. CXCR2 expression was downregulated in neutrophils of IPF patients. These findings indicate that CXCL12, CAV1, and CXCR2 are novel diagnostic biomarkers for IPF and may participate in the occurrence and development of the disease by regulating cellular senescence. Thus, our findings suggest a new therapeutic strategy IPF treatment.