Immune subtype as a moderator of the prognostic significance of mutations in lung adenocarcinoma: a TCGA data analysis

Introduction. Lung adenocarcinoma is a genetically and immunologically heterogeneous disease, with key mutations affecting prognosis and response to therapy. This study aimed to evaluate the impact of individual and combined mutations in six key genes (TP53, KRAS, STK11, KEAP1, EGFR, BRAF) on overall survival in patients with lung adenocarcinoma, considering the tumor’s immune subtype. Methods. A cohort of 390 patients from the TCGA-LUAD dataset was analyzed using survival models stratified by immune subtype: high, medium, and low. Kaplan–Meier analysis and multivariable Cox regression were used for statistical analysis. A p-value <0.05 was considered statistically significant. Results. Significantly better median overall survival was observed in the high immune subtype group (59.7 months) compared to medium (45.2 months) and low (29.9 months) subtypes (p = 0.0017). The STK11 mutation and KRAS+TP53 co-mutation were the strong predictors of poor prognosis in the high immune subtype. In the medium immune subtype, KRAS+STK11, KRAS+KEAP1, and especially STK11+KEAP1 co-mutations were associated with markedly increased mortality risk. No statistically significant predictors were identified in the low immune subtype, although KRAS mutation showed a trend toward worse outcomes. Conclusions. The prognostic impact of genetic mutations in lung adenocarcinoma is significantly modulated by the tumor’s immune context.