Identification of lung adenocarcinoma subtypes and a prognostic signature based on activity changes of the hallmark and immunologic gene sets

Abstract

Background: Lung adenocarcinoma (LUAD) has a complex tumor heterogeneity. This study aimed to identify LUAD subtypes and build a reliable prognostic signature based on the activity changes of the hallmark and immunologic gene sets. Methods: Changes in the activities of the hallmark and immunologic gene sets were analyzed based on The Cancer Genome Atlas (TCGA)-LUAD dataset, followed by identification of prognosis-related differential gene sets (DGSs) and their related LUAD subtypes. Survival analysis, correlation with clinical characteristics, and immune microenvironment assessment for subtypes were performed. Moreover, the DGSs among different subtypes were identified, followed by the construction and evaluation of a prognostic risk score model and nomogram. The tumor mutation burden (TMB) of different risk groups wascompared. Results: Two LUAD subtypes were identified based on the activity changes of the hallmark and immunologic gene sets. Cluster 2 had worse prognosis, more advanced tumorand clinical stages, and higher immune infiltration than cluster 1. Moreover, a prognostic risk score signaturewas established using two LUAD subtype-related DGSs, which could stratify patients at different risk levels. A shorter survival time and higher TMB levels were observed in the high-risk patients. The established nomogram accurately predicted the survival outcomes. Conclusions: Our findings revealed that our constructed prognostic signature could accurately predict the survival outcomes and immune microenvironment of patients with LUAD, which was helpful in predicting the prognosis and guiding personalized therapeutic strategies for LUAD.