Abstract
This study investigates the mechanisms of Osimertinib resistance in lung adenocarcinoma (LUAD) by identifying prognostic genes associated with SUMOylation. We performed differential expression analysis to identify differentially expressed genes (DEGs) in LUAD samples, Osimertinib-tolerant cell samples and SUMOylation-related genes (SRGs). Utilizing Cox regression and LASSO regression, we developed a prognostic model that highlighted five key prognostic genes-BIRC5, AURKA, BLM, NR3C2, and NDC1. These genes were significantly associated with LUAD progression, revealing their predominant expression in epithelial cells, which play a vital role in tumor development. Furthermore, we explored the biological functions and signaling pathways linked to these prognostic genes, discovering that their expression levels and corresponding risk scores could serve as indicators of CD4 T cell and memory B cell activation. The enriched signaling pathways in LUAD were regulated by ubiquitin-related small modifiers, highlighting the complex interplay between SUMOylation and tumor biology. Our findings suggest the important role of SUMOylation-regulated genes in LUAD progression and Osimertinib resistance, suggesting their potential as valuable biomarkers for prognosis and therapeutic targets to enhance treatment strategies for patients with EGFR-mutant lung adenocarcinoma.