Abstract
Lung adenocarcinoma (LUAD), the most common non-small cell lung cancer subtype, often presents with subtle early symptoms leading to delayed diagnosis. Ferroptosis, a cell death process associated with iron metabolism dysregulation, has been linked to cancer onset, progression, and treatment resistance. Thus, identifying ferroptosis-related genes may offer novel insights for LUAD therapy. In this study, we employed the random walk with restart (RWR) algorithm on the LUAD protein-protein interaction (PPI) network to predict ferroptosis-related target genes. Gene set enrichment analysis (GSEA) explored the relationship between XBP1 and ferroptosis, while tumor microenvironment analysis evaluated the correlation between XBP1 expression and immune cell infiltration. External cohorts validation was performed using the GSE118370, GSE68465, and TCGA-LUAD datasets. Our analysis identified XBP1 as a potential ferroptosis-related gene in LUAD. GSEA confirmed a strong association between XBP1 and the ferroptosis process, along with its involvement in the tumor microenvironment, and external cohorts demonstrated its high expression and significant correlation with immune cell infiltration in LUAD tissues. These findings suggest that XBP1 plays a key role in LUAD development and progression, providing new perspectives for precision therapies targeting the ferroptosis pathway.