Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of lung adenocarcinoma

BackgroundLung adenocarcinoma (LUAD) is the most common primary lung cancer, and increasing evidence indicates the clinical importance of the microenvironment in LUAD. Tumor-infiltrating immune cells play an important role in promoting or inhibiting tumor growth. This study aimed to identify immune-related prognostic genes that were associated with the LUAD microenvironment. MethodsWe used the "estimate" R package to calculate the immune/stromal scores of each sample of GSE72094 based on the ESTIMATE algorithm. Then we looked up relationships between patients characteristics and immune/stromal scores. After that, we divided the samples into two groups: high and low scores, identified the common differentially expressed genes (DEGs), and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) on the common DEGs. After conducting the overall survival analysis of the common DEGs, prognostic genes were harvested. Then we constructed the protein-protein interaction network and performed the enrichment of GO and KEGG for the prognostic genes. Crucial prognostic genes were obtained after validating in two independent data sources (GSE68465 and TIMER). Finally, we investigated the immune correlates of the crucial prognostic genes based on the TIMER. ResultsImmune scores did not vary with gender, age, smoking history, tumor stage, and EGFR status, but vary with the status of KRAS, STK11, and TP53. For the stromal scores, only the status of STK11 and TP53 mattered. Reduced immune score predicted poor prognosis of LUAD. 357 common DEGs were found, of which 108 were identified as prognostic genes after overall survival analysis. GO and KEGG analysis found that common DEGs and prognostic genes were both mainly involved in immune-related items. After validation in two independent data sources, 12 genes were validated to be crucial prognostic genes linked to prognosis. After investigated the TIMER, all 12 genes were correlated with the main immune cell types. Conclusion12 immune-related prognostic genes were discovered relating to the microenvironment in LUAD. These findings suggest that the composition of the tumor microenvironment affects the clinical outcomes of LUAD, and it may provide a basis for the development of novel prognostic biomarkers and immunotherapy for LUAD.