Abstract
BackgroundCD8+ T cells are one of the central effector cells in the immune microenvironment. CD8+ T cells play a vital role in the development and progression of lung adenocarcinoma (LUAD). This study aimed to explore the key genes related to CD8+ T-cell infiltration in LUAD and to develop a novel prognosis model based on these genes.MethodsWith the use of the LUAD dataset from The Cancer Genome Atlas (TCGA), the differentially expressed genes (DEGs) were analyzed, and a co-expression network was constructed by weighted gene co-expression network analysis (WGCNA). Combined with the CIBERSORT algorithm, the gene module in WGCNA, which was the most significantly correlated with CD8+ T cells, was selected for the subsequent analyses. Key genes were then identified by co-expression network analysis, protein–protein interactions network analysis, and least absolute shrinkage and selection operator (Lasso)-penalized Cox regression analysis. A risk assessment model was built based on these key genes and then validated by the dataset from the Gene Expression Omnibus (GEO) database and multiple fluorescence in situ hybridization experiments of a tissue microarray.ResultsFive key genes (MZT2A, ALG3, ATIC, GPI, and GAPDH) related to prognosis and CD8+ T-cell infiltration were identified, and a risk assessment model was established based on them. We found that the risk score could well predict the prognosis of LUAD, and the risk score was negatively related to CD8+ T-cell infiltration and correlated with the advanced tumor stage. The results of the GEO database and tissue microarray were consistent with those of TCGA. Furthermore, the risk score was higher significantly in tumor tissues than in adjacent lung tissues and was correlated with the advanced tumor stage.ConclusionsThis study may provide a novel risk assessment model for prognosis prediction and a new perspective to explore the mechanism of tumor immune microenvironment related to CD8+ T-cell infiltration in LUAD.
Highlights
Lung adenocarcinoma (LUAD) is the most common type of lung cancer, accounting for 40% of all lung cancers [1,2,3]
After comparing the expressions of LUAD tissues with those of normal tissues in The Cancer Genome Atlas (TCGA)-LUAD cohort, we identified 8,807 Differentially expressed gene (DEG), including 2,172 upregulated genes and 6,635 downregulated genes (Figures 2A, B)
We found that the risk score was significantly negatively correlated to the infiltration of CD8+ T cells, which validated our bioinformatics analysis (Figure 11A)
Summary
Lung adenocarcinoma (LUAD) is the most common type of lung cancer, accounting for 40% of all lung cancers [1,2,3]. CD8+ T cells are central effector cells in the tumor microenvironment, and previous studies have reported that highly infiltrating CD8+ T cells are beneficial to prognosis in most tumors, including LUAD [9,10,11,12,13,14]. The mechanism of CD8+ T-cell infiltration in the tumor microenvironment in LUAD is still unclear. Identifying novel biomarkers related to CD8+ T-cell infiltration may help explore the immune infiltration mechanism in LUAD. CD8+ T cells play a vital role in the development and progression of lung adenocarcinoma (LUAD). This study aimed to explore the key genes related to CD8+ T-cell infiltration in LUAD and to develop a novel prognosis model based on these genes
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