Identification of lung adenocarcinoma subtypes and predictive signature for prognosis, immune features, and immunotherapy based on immune checkpoint genes

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Bin You¹  Bin Hu¹  Linbin Hua¹  Jiashu Ge¹  Xin Li¹  Jiyue Wu²  Wei Wang² 

[1] Department of Thoracic Surgery, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, China;Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China;

关键词: lung adenocarcinoma (LUAD);    immune checkpoints;    prognosis;    immunotherapy;    individualized treatment;   

DOI  :  10.3389/fcell.2023.1060086

 received in 2022-10-02, accepted in 2023-05-02,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background: Lung adenocarcinoma (LUAD) is the most common variant of non–small cell lung cancer (NSCLC) across the world. Recently, the rapid development of immunotherapy has brought a new dawn for LUAD patients. Closely related to the tumor immune microenvironment and immune cell functions, more and more new immune checkpoints have been discovered, and various cancer treatment studies targeting these novel immune checkpoints are currently in full swing. However, studies on the phenotype and clinical significance of novel immune checkpoints in LUAD are still limited, and only a minority of patients with LUAD can benefit from immunotherapy.Methods: The LUAD datasets were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, and the immune checkpoints score of each sample were calculated based on the expression of the 82 immune checkpoints-related genes (ICGs). The weighted gene co-expression network analysis (WGCNA) was used to obtain the gene modules closely related to the score and two different LUAD clusters were identified based on these module genes by the Non-negative Matrix Factorization (NMF) Algorithm. The differentially expressed genes between the two clusters were further used to construct a predictive signature for prognosis, immune features, and the response to immunotherapy for LUAD patients through a series of regression analyses.Results: A new immune checkpoints-related signature was finally established according to the expression of 7 genes (FCER2, CD200R1, RHOV, TNNT2, WT1, AHSG, and KRTAP5-8). This signature can stratify patients into high-risk and low-risk groups with different survival outcomes and sensitivity to immunotherapy, and the signature has been well validated in different clinical subgroups and validation cohorts.Conclusion: We constructed a novel immune checkpoints-related LUAD risk assessment system, which has a good predictive ability and significance for guiding immunotherapy. We believe that these findings will not only aid in the clinical management of LUAD patients but also provide some insights into screening appropriate patients for immunotherapy.

【 授权许可】

Unknown   
Copyright © 2023 Hua, Wu, Ge, Li, You, Wang and Hu.