Identification of Key Genes and Clinical Feature Analyses of Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinoma

Background: Lung adenocarcinoma (LUAD) is a prevalent and aggressive form of lung cancer, characterized by late-stage diagnosis, high metastatic potential, and recurrence. Epidermal growth factor receptor (EGFR) mutations are commonly observed in LUAD. However, other key genes associated with EGFR mutations in LUAD remain to be clarified. Therefore, this study aims to identify key genes associated with EGFR mutations in LUAD and explore their potential mechanisms. Methods: The Cancer Genome Atlas (TCGA)-LUAD and LUAD sequencing datasets were utilized to compare survival outcomes between EGFR-mutant and wild-type groups. Differentially expressed genes (DEGs) were identified by comparing these groups within TCGA-LUAD, followed by algorithmic analysis to pinpoint key genes. Prognostic analyses were integrated with clinical features, resulting in the construction and validation of a nomogram. Further investigations included gene set enrichment analysis, tumor mutational burden evaluation, immune checkpoint profiling, immune cell infiltration analysis, and drug sensitivity testing. Results: The EGFR-mutant group exhibited significantly reduced survival rates ( p < 0.05); a total of 654 DEGs were identified between the EGFR-mutant group and the wild-type group. Key genes including Apolipoprotein B, C-reactive protein, kininogen 1, F2, and Alpha-2-HS-glycoprotein (AHSG) were predominantly involved in complement and coagulation cascades, ribosomal function, and cytochrome P450 metabolism. Both T and N stages were found to be independent prognostic factors and were incorporated into a highly predictive nomogram. Three immune cell types—neutrophils, activated CD4 + T cells—and five immune checkpoints were identified. Mutually exclusive and co-occurrence mutation analysis revealed a mutually exclusive relationship between Titin (TTN) and EGFR. Additionally, there were significant differences in the half-maximal inhibitory concentration values of 49 drugs between the mutant and wild groups. Conclusion: This study identified five key genes linked to EGFR mutations in LUAD and analyzed their clinical features, providing new perspectives for its prevention and treatment.