IFNγ-associated gene signature as a potential prognostic biomarker of survival and immunotherapy response in lung adenocarcinoma

Background. Lung adenocarcinoma is the most common form of non-small cell lung cancer and is associated with high mortality. Identifying molecular markers capable of predicting the effectiveness of immunotherapy remains a pressing challenge in modern oncology. One such marker is the IFNγ-associated gene signature, which reflects the level of activation within the tumor immune microenvironment. Purpose – to evaluate the association between the expression of the IFNγ-associated gene signature and overall survival in patients with lung adenocarcinoma, as well as to determine its potential prognostic value. Materials and Methods. Data from 390 patients were analyzed from the open oncological database The Cancer Genome Atlas (TCGA-LUAD project), including clinical, mutational, and transcriptomic characteristics. Expression of the IFNγ signature was calculated as the average of the log-transformed expression values of 10 genes (CXCL9, CXCL10, CXCL11, IDO1, IRF9, CCR5, STAT1, PRF1, IFNG, HLA-DRA). High and low expression groups were defined based on ROC analysis. Statistical analyses were performed using Kaplan–Meier estimates, chi-squared tests, and Cox proportional hazards models. Results. Patients with high expression of the IFNγ-associated gene signature (n = 189) had a significantly longer median overall survival (47.4 vs. 41.2 months, p = 0.0438). Higher expression was associated with female sex (62.4% vs. 46.3%, p = 0.001) and stage I disease (p = 0.034). KEAP1 mutations were more frequent in the low-expression group (23.9% vs. 12.2%, p = 0.003), while EGFR mutations were more common in the high-expression group (20.1% vs. 9.5%, p = 0.003). In multivariate analysis, the only independent predictor of poorer prognosis was the STK11 mutation (HR = 1.52; p = 0.045). Conclusions. The IFNγ-associated gene signature correlates with more favorable clinicopathological features and overall survival; however, its independent prognostic value requires further investigation.