Li Hongzhi, Gao Xian, Chen Chengde, Cui Zhongfeng, Cao Xiaojiu, Su Jing, Li Guangming
Department of Tuberculosis Diseases, The Sixth People's Hospital of Zhengzhou, Zhengzhou, 450000, Henan, China.
Department of Clinical Laboratory, The Sixth People's Hospital of Zhengzhou, Zhengzhou, 450000, Henan, China.
Eur J Med Res. 2025 Nov 27;30(1):1301. doi: 10.1186/s40001-025-03544-w.
Lung adenocarcinoma (LUAD) is a leading cause of cancer deaths. Given that traditional pathologic features to diagnose LUAD do not fully reflect the biological differences in patients, the search for novel biomarkers is necessary.
In this study, we obtained immune-related genes (IRGs) from ImmPort and performed cluster analysis on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to mine LUAD subtypes with different immune characteristics. Quantitative analysis of IRGs was performed by single-sample gene set enrichment analysis (ssGSEA). Based on the univariate cox and LASSO regression methods, we screened the characteristic genes that significantly affected LUAD and built the model based on the RiskScore coefficients. The relative expressions of characteristic genes in LUAD were determined using qRT-PCR. Transwell and wound healing assays were utilized to verify the practical regulation of these genes on the migration and invasion levels of LUAD. Correlations were established between RiskScore and LUAD drug sensitivity by oncoPredict.
We acquired three LUAD subtypes and demonstrated heterogeneous IRGs scores and clinical features. The molecular subtypes were differentially enriched in bile acid metabolism, fatty acid metabolism, and ECM-receptor interaction. This study identified seven genes (MS4A1, EXO1, CPS1, ZNF750, S100P, NT5E, KCNN4) as a signature affecting prognosis, from the differentially expressed genes (DEGs) among the molecular subtypes, and constructed a RiskScore for the prognosis of LUAD. Cellular experiments verified that 6 of 7 characteristic genes were expression dysregulation in LUAD cell line. Silencing of EXO1 significantly suppressed the migration and invasion of LUAD cell lines. RiskScore and immune checkpoints such as CD276, TNFSF4, and TNFSF9 showed a positive correlation.
This study identified three LUAD subtypes with distinct immune characteristics and constructed a seven-gene prognostic model. This model correlates with immune checkpoint and chemotherapy sensitivity, providing new targets and strategies for clinical diagnosis and treatment.
