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Identification of an Immunologic Signature of Lung Adenocarcinomas Based on Genome-Wide Immune Expression Profiles.

ABSTRACT: Background: Lung cancer is one of the most common types of cancer, and it has a poor prognosis. It is urgent to identify prognostic biomarkers to guide therapy. Methods: The immune gene expression profiles for patients with lung adenocarcinomas (LUADs) were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). The relationships between the expression of 45 immune checkpoint genes (ICGs) and prognosis were analyzed. Additionally, the correlations between the expression of 45 biomarkers and immunotherapy biomarkers, including tumor mutation burden (TMB), mismatch repair defects, neoantigens, and others, were identified. Ultimately, prognostic ICGs were combined to determine immune subgroups, and the prognostic differences between these subgroups were identified in LUAD. Results: A total of 11 and nine ICGs closely related to prognosis were obtained from the GEO and TCGA databases, respectively. CD200R1 expression had a significant negative correlation with TMB and neoantigens. CD200R1 showed a significant positive correlation with CD8A, CD68, and GZMB, indicating that it may cause the disordered expression of adaptive immune resistance pathway genes. Multivariable Cox regression was used to construct a signature composed of four prognostic ICGs (IDO1, CD274, CTLA4, and CD200R1): Risk Score = -0.002^* IDO1+0.031^* CD274-0.069^* CTLA4-0.517^* CD200R1. The median Risk Score was used to classify the samples for the high- and low-risk groups. We observed significant differences between groups in the training, testing, and external validation cohorts. Conclusion: Our research provides a method of integrating ICG expression profiles and clinical prognosis information to predict lung cancer prognosis, which will provide a unique reference for gene immunotherapy for LUAD.

SUBMITTER: Ling B

PROVIDER: S-EPMC7832236 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Identification of an Immunologic Signature of Lung Adenocarcinomas Based on Genome-Wide Immune Expression Profiles.

Ling Bo B Ye Guangbin G Zhao Qiuhua Q Jiang Yan Y Liang Lingling L Tang Qianli Q

Frontiers in molecular biosciences 20210111

<b>Background:</b> Lung cancer is one of the most common types of cancer, and it has a poor prognosis. It is urgent to identify prognostic biomarkers to guide therapy. <b>Methods:</b> The immune gene expression profiles for patients with lung adenocarcinomas (LUADs) were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). The relationships between the expression of 45 immune checkpoint genes (ICGs) and prognosis were analyzed. Additionally, the correlations betwee ...[more]

PMID: 33505988

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Project description:BACKGROUND:Lung cancer is the worldwide leading cause of death from cancer. Tobacco usage is the major pathogenic factor, but all lung cancers are not attributable to smoking. Specifically, lung cancer in never-smokers has been suggested to represent a distinct disease entity compared to lung cancer arising in smokers due to differences in etiology, natural history and response to specific treatment regimes. However, the genetic aberrations that differ between smokers and never-smokers' lung carcinomas remain to a large extent unclear. METHODS:Unsupervised gene expression analysis of 39 primary lung adenocarcinomas was performed using Illumina HT-12 microarrays. Results from unsupervised analysis were validated in six external adenocarcinoma data sets (n=687), and six data sets comprising normal airway epithelial or normal lung tissue specimens (n=467). Supervised gene expression analysis between smokers and never-smokers were performed in seven adenocarcinoma data sets, and results validated in the six normal data sets. RESULTS:Initial unsupervised analysis of 39 adenocarcinomas identified two subgroups of which one harbored all never-smokers. A generated gene expression signature could subsequently identify never-smokers with 79-100% sensitivity in external adenocarcinoma data sets and with 76-88% sensitivity in the normal materials. A notable fraction of current/former smokers were grouped with never-smokers. Intriguingly, supervised analysis of never-smokers versus smokers in seven adenocarcinoma data sets generated similar results. Overlap in classification between the two approaches was high, indicating that both approaches identify a common set of samples from current/former smokers as potential never-smokers. The gene signature from unsupervised analysis included several genes implicated in lung tumorigenesis, immune-response associated pathways, genes previously associated with smoking, as well as marker genes for alveolar type II pneumocytes, while the best classifier from supervised analysis comprised genes strongly associated with proliferation, but also genes previously associated with smoking. CONCLUSIONS:Based on gene expression profiling, we demonstrate that never-smokers can be identified with high sensitivity in both tumor material and normal airway epithelial specimens. Our results indicate that tumors arising in never-smokers, together with a subset of tumors from smokers, represent a distinct entity of lung adenocarcinomas. Taken together, these analyses provide further insight into the transcriptional patterns occurring in lung adenocarcinoma stratified by smoking history.

Dataset Information

Identification of an Immunologic Signature of Lung Adenocarcinomas Based on Genome-Wide Immune Expression Profiles.

Publications

Identification of an Immunologic Signature of Lung Adenocarcinomas Based on Genome-Wide Immune Expression Profiles.

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