A Novel Immune-Prognosis Index Predicts the Benefit of Lung Adenocarcinoma Patients

Background: Constructed an immune-prognosis index (IPI) and divided lung adenocarcinoma (LUAD) patients into different subgroups according to IPI score, describe the molecular and immune characteristics of patients between different IPI subgroups, and explore their response to immune checkpoint blockade (ICB) treatment. Methods: Based on the transcriptome profile of LUAD patients in TCGA and immune gene sets from ImmPort and InnateDB, 15 hub immune genes were identified through correlation and Bayesian causal network analysis. Then, IPI was constructed with 5 immune genes by using COX regression analysis and verified with external datasets (GSE30219, GSE37745, GSE68465, GSE126044 and GSE135222). Finally, the characteristics and the response to ICB treatment of LUAD patients between two different IPI subgroups were analyzed. Results: IPI was constructed based on the expression of 5 genes, including A2M, ADRB1, ADRB2, VIPR1 and PTH1R. IPI-high LUAD patients have a better overall survival than IPI-low LUAD patients, consistent with the results in the GEO cohorts. The comprehensive results showed that patients in the IPI-high subgroup were exhibited characters as metabolism-related signaling pathways activation, lower TP53 and TTN mutation rate, more infiltrations of CD8 T cells, dendritic cells and macrophages M1, especially earned more benefit from ICB treatment. In contrast, patients in the IPI-low subgroup were exhibited characters as p53 signaling pathways activation, higher TP53 and TTN mutation rate, more infiltrations of resting memory CD4 T cells, macrophages M2, immune-suppressive response and less benefit from ICB treatment. Conclusion: IPI is a potentially valuable prognostic evaluation method for LUAD, which works well in the benefit predicting of LUAD patients within ICB treatment.