Analyzing the characteristics of immune cell infiltration in lung adenocarcinoma via bioinformatics to predict the effect of immunotherapy

被引:0
作者
Yi Liao
Dingxiu He
Fuqiang Wen
机构
[1] West China Hospital of Sichuan University,State Key Laboratory of Biotherapy of China, Division of Pulmonary Diseases, Department of Respiratory and Critical Care Medicine
来源
Immunogenetics | 2021年 / 73卷
关键词
Lung adenocarcinoma; Immunotherapy; Immune cell infiltration; TCGA; Bioinformatics;
D O I
暂无
中图分类号
学科分类号
摘要
Recent studies have shown that tumor immune cell infiltration (ICI) is associated with immunotherapy sensitivity and the prognosis of lung adenocarcinoma (LUAD). However, the immunoinfiltrative landscape of LUAD has not been elucidated. We propose two computational algorithms to unravel the ICI landscape to evaluate the efficacy of immunotherapy in LUAD patients. The raw data of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed. After merging these datasets and removing the batch differences, we used the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm to obtain the immune cell content of all the samples. The unsupervised consistency clustering algorithm was used to analyze the ICI subtypes, and three subgroups were obtained. In addition, the unsupervised consistency clustering algorithm was used to analyze the differentially expressed genes (DEGs) of the ICI subtypes and obtain three ICI gene clusters. Finally, the ICI score was determined by using principal component analysis (PCA) for the gene signature. The ICI score of LUAD patients ranged from − 32.26 to 12.89 and represents the prognosis and the response to immunotherapy. High ICI scores were characterized by the T cell receptor signaling pathway, B cell receptor signaling pathway, and natural killer cell–mediated cytotoxicity, suggesting that some immune cells were activated and had increased activity, which may be the cause of the better prognosis for patients with high ICI scores. Additionally, patients with higher ICI scores showed a significant immune therapeutic advantage and clinical benefit. This study shows that the ICI score may be a potent prognostic biomarker and predictor of therapy with immune checkpoint inhibitors.
引用
收藏
页码:369 / 380
页数:11
相关论文
共 240 条
[1]  
Ahmed F(2019)Integrated network analysis reveals FOXM1 and MYBL2 as key regulators of cell proliferation in non-small cell lung cancer Front Oncol 9 1011-2940
[2]  
Ayers M(2017)IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade J Clin Investig 127 2930-1280
[3]  
Lunceford J(2017)Molecular-subtype-specific biomarkers improve prediction of prognosis in colorectal cancer Cell Rep 19 1268-800
[4]  
Nebozhyn M(2016)The role of tumor-infiltrating lymphocytes in development, progression, and prognosis of non–small cell lung cancer J Thorac Oncol 11 789-345
[5]  
Bramsen JB(2015)Subtype-specific metagene-based prediction of outcome after neoadjuvant and adjuvant treatment in breast cancer Clin Cancer Res 22 337-7259
[6]  
Rasmussen MH(2004)X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization Clin Cancer Res 10 7252-124
[7]  
Ongen H(2018)Rare targetable drivers (RTDs) in non-small cell lung cancer (NSCLC): outcomes with immune check-point inhibitors (ICPi) Lung Cancer 124 117-151
[8]  
Bremnes RM(2019)Engineering nanoparticles for targeted remodeling of the tumor microenvironment to improve cancer immunotherapy Theranostics 9 126-1684
[9]  
Busund LT(2018)Five-year follow-up of nivolumab in previously treated advanced non–small-cell lung cancer: results from the CA209-003 study J Clin Oncol 36 1675-53
[10]  
Kilvær TL(2019)The clinical role of the TME in solid cancer Br J Cancer 120 45-2608