Identification of common genetic features and pathways involved in pulmonary lymphangioleiomyomatosis and ER-positive breast cancer

Accumulating evidence suggests that patients with pulmonary lymphangioleiomyomatosis (PLAM) have a markedly higher prevalence of breast cancer (BC) than the general population. However, the underlying pathophysiological mechanisms remain unclear. Therefore, in this study, we employed a bioinformatics approach to understand the association between PLAM and estrogen receptor (ER)-positive BC. The PLAM (GSE12027) and ER-positive BC (GSE42568, GSE29044, and GSE29431) datasets were obtained from the Gene Expression Omnibus database, and GEO2R was used to identify common differentially expressed genes (DEGs) between them. Functional annotation was performed, and a protein–protein interaction (PPI) network was constructed. Hub genes were identified and verified using western blotting and immunohistochemistry. We conducted an immune infiltration analysis; based on the results, selected 102 common DEGs for follow-up analysis. Functional analyses revealed that the DEGs were mostly enriched in cell proliferation, gene expression regulation, and tumor-related pathways. Four hub genes—ESR1, IL6, PLA2G4A, and CAV1—were further analyzed, and CAV1 was revealed to be associated with clinical outcomes and immune infiltration in ER-positive BC. This study proposes a common, possible pathogenesis of PLAM and ER-positive BC. These common pathways and pivotal genes may provide new directions for further mechanistic studies.