Systemic immune microenvironment and regulatory network analysis in patients with lung adenocarcinoma.
Transl Cancer Res
; 10(6): 2859-2872, 2021 Jun.
Article
em En
| MEDLINE
| ID: mdl-35116596
ABSTRACT
BACKGROUND:
This study applied a complex bioinformatics analysis to explore the hub regulators and immune network to further elucidate the molecular mechanisms of lung adenocarcinoma (LUAD) immune regulation.METHODS:
LUAD immunological microenvironment features and microenvironment-related differential expression genes (DEGs) were identified by ESTIMATE algorithm and linear models for microarray analyses (LIMMA), respectively. CIBERSORT and Igraph algorithms were applied to construct the LUAD-related immunocyte infiltration and regulatory network. Kaplan-Meier survival analysis, and univariate and multivariate Cox analysis were used to predict independent risk factors and screen for the hub genes. In addition, hub genes-correlated gene set enrichment analysis (GSEA), tumor mutation burden (TMB), and clinic pathological relation analyses were also performed.RESULTS:
Stromal, immune, and microenvironment comprehensive features (ESTIMATE score) were associated with overall survival (OS) in LUAD patients (all, P<0.05). T-cell activation, chemokine activity, and immune effect or dysfunction gene ontology maps were associated with the LUAD immune microenvironment. The immune infiltration cell subtypes mast cells (masT-cells) resting [The Cancer Genome Atlas (TCGA) P=0.01; Gene Expression Omnibus (GEO) P=1.79e-05] and activated T-cells (CD4 memory) (TCGA P<0.01; GEO P=8.52e-05) were found to have an important role in the immune cell regulatory network. Finally, ITGAL [univariate hazard ratio (HR) =0.80, 95% confidence interval (CI) 0.69-0.93, P<0.01; multivariate HR =0.59, 95% CI 0.40-0.86, P=0.01] and KLRB1 (univariate HR =0.78, 95% CI 0.69-0.89, P<0.01; multivariate HR =0.72, 95% CI 0.58-0.90, P<0.01) were correlated with the T-cell receptor signaling pathway and anaplastic lymphoma kinase (ALK) fusion (ITGAL P=0.034; KLRB1 P=0.050), and were considered as candidate biomarkers. A significant relation between KLRB1 expression level and TMB (P=3.6e-05) was identified, while no relation was detected for ITGAL (P=0.11).CONCLUSIONS:
The T-cell activation and activated T-cell (CD4 memory) pathways were predominantly involved in LUAD immune microenvironment regulation. The expression levels of ITGAL and KLRB1 were significantly correlated with the T-cell receptor signaling pathway and LUAD TMB, and were independent risk factors for OS.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Transl Cancer Res
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China