AUTHOR=Du Minjun , Liang Yicheng , Liu Zixu , Li Xingkai , Liang Mei , Zhou Boxuan , Gao Yushun 

TITLE=Identification of Key Genes Related to CD8+ T-Cell Infiltration as Prognostic Biomarkers for Lung Adenocarcinoma

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.693353

DOI=10.3389/fonc.2021.693353

ISSN=2234-943X

ABSTRACT=Background
CD8+ 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 develop a novel prognosis model based on these genes.

Methods
Using 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 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. 

Results
Five key genes (MZT2A, ALG3, ATIC, GPI, 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 Gene Expression Omnibus (GEO) database and tissue microarray were consistent with that of TCGA. Furthermore, the risk score  higher significantly in tumor tissues than inadjacent lung tissues and was correlated with the advanced tumor stage.  

Conclusions
This 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.