Identification of Key Genes and Biological Pathways of Tumor-infiltrating CD8+ T Cell in Lung Adenocarcinoma

Abstract

Background: The immune microenvironment of lung cancer is complex, and T-cell tolerance is a primary mechanism of immune evasion. Tumor-derived exosomes (TEX) miRNAs regulate immune cells in tumor microenvironment (TME), contributing to tumor immune suppression. However, the underlying mechanisms remain unclear.Methods: TEX miRNA expression dataset (GSE111803) and CD8+ T cells mRNA expression profile (GSE90728) in lung adenocarcinoma (LUAD) were downloaded from Gene Expression Omnibus (GEO). The differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were analyzed. The intersection of target genes of DEMs and DEGs was defined as the overlapped target genes. We performed the function and pathway analysis for DEGs and the overlapped genes by the DAVID tool and constructed a protein-protein interaction (PPI) network to screen modules and hub genes. Results: In total, 7 DEMs (5 upregulated and two downregulated miRNAs) and 672 DEGs (219 upregulated and 453 downregulated genes) were identified, then 185 overlapped genes for upregulated DEMs were selected for further analysis. GO analysis indicated the DEGs were mainly enriched in positive regulation of B cell activation, innate immune, while the overlapped genes were primarily involved in regulation of immune response. The pathway analysis suggested DEGs were primarily enriched in cytokine-cytokine receptor interaction, while the overlapped genes were primarily enriched in osteoclast differentiation. The PPI network revealed three significant modules for DEGs and the overlapped genes sets. These modules genes were mainly enriched in cell cycle, chemokine signaling pathway, and cytokine-cytokine receptor interaction, respectively.Conclusions: These results preliminarily revealed the mRNA expression profiles and the molecular regulatory mechanism of TEX miRNA regulated tumor immune response in LUAD.