Basal and AT2 cells promote IPF-lung cancer co-occurrence via EMT: Single-cell analysis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung disease. With IPF, the probability of complication with lung cancer (LCA) increases considerably, and the prognosis is worse than that of simple IPF. To understand the pathological mechanisms and molecular pathways shared by these two diseases, we used the single-cell analysis from the Gene Expression Omnibus (GEO) database, and find that basal cells (BCs) and alveolar type 2 cells (AT2 cells) are important components of lung epithelial cells. Changes in molecular pathways in BCs and AT2 cells may be involved in the common pathogenesis of IPF and LCA. KRT17 and S100A14 in BCs may promote the IPF co-occurrence with LCA by mediating the EMT. WFDC2 and KRT19 may be the elements in AT2 cells that activate the EMT process to promote IPF co-occurrence with LCA. In both IPF and LCA, FN1-WNT axis may be involved in the interaction between BCs and AT2 cells. Importantly, the results of immunofluorescence colocalization experiments on tissue samples from patients with IPF and LCA were consistent with these conclusions. Basal-macrophage interactions may have also induced the IPF co-occurrence with LCA via the CYBA-ERK1/2 axis. The regulation of M2 macrophage polarization by JUN/SOD2-glycolysis axis may therefore be involved in the co-morbidity mechanism of IPF and LCA. Therefore, our results suggest that molecular changes in BCs, AT2 cells and macrophages may play important roles in the pathogenesis of IPF co-occurrence with LCA, and the cellular interactions between these cells may be critical for the progression of both diseases.