Identification of immune cell-related biomarkers in lung adenocarcinoma using weighted gene co-expression network analysis
- VernacularTitle:肺腺癌中加权基因共表达网络鉴定免疫细胞相关生物标志物
- Author:
Dongyuan HE
1
;
Bo CHEN
1
;
Jingyao LIANG
1
;
Haibo YE
1
;
Xiaoxing YI
1
;
Guangni LIANG
1
Author Information
1. Department of Thoracic Surgery, The First People’s Hospital of Yulin, Yulin, 537000, Guangxi, P. R. China
- Publication Type:Journal Article
- Keywords:
The Cancer Genome Atlas;
lung adenocarcinoma;
weighted gene co-expression network analysis;
immunotherapy;
biomarker;
prognosis;
immune infiltration
- From:
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery
2026;33(05):751-758
- CountryChina
- Language:Chinese
-
Abstract:
Objective To identify immune cell-related biomarkers in lung adenocarcinoma (LUAD) using weighted gene co-expression network analysis (WGCNA). Methods Based on data from The Cancer Genome Atlas (TCGA) database, a gene co-expression network was constructed for the TCGA-LUAD dataset using the "WGCNA" R package, and genes were clustered into different modules. Concurrently, the Estimation of STromal and Immune cells in MAlignant Tumours using Expression data (ESTIMATE) algorithm was applied to the tumor samples in the TCGA-LUAD dataset. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to evaluate the biological functions of genes within the most significantly correlated module. Candidate hub genes from the key module were intersected with a protein-protein interaction (PPI) network to identify the final hub genes. The prognostic performance of these hub genes and their correlation with immune cell infiltration were validated using Kaplan-Meier curves and the Tumor IMmune Estimation Resource (TIMER) algorithm. Finally, a multivariate Cox regression analysis was conducted on the identified hub genes to construct a prognostic risk model. Results In the co-expression network, the brown module was found to be highly correlated with the ImmuneScore, StromalScore, and ESTIMATE Score. Five immune-related hub genes were identified: CD53, PLEK, SPI1, IL10RA, and C3AR1. Enrichment analysis of the brown module revealed that its genes were primarily enriched in GO terms such as "regulation of innate immune response" and KEGG pathways like the "NF-kappa B signaling pathway". Furthermore, the expression levels of these five hub genes were significantly and positively correlated with the infiltration abundance of various immune cells. The immune relevance of the model was validated by the Immunophenoscore (IPS) and the Tumor Immune Dysfunction and Exclusion (TIDE) score. Moreover, the established RiskScore demonstrated significant potential in predicting the response to immunotherapy. Conclusion These five immune-related key genes may serve as novel and effective potential therapeutic targets for LUAD immunotherapy, facilitating the development of personalized diagnosis and treatment strategies for patients with LUAD.
