Evidence map›Paper›PMID 41310864›Full record

ArticleEuropean journal of medical research2025

Molecular subtyping and a seven-gene immune signature reveal heterogeneity in tumor microenvironment and prognosis of lung adenocarcinoma.

Hongzhi Li, Xian Gao, Chengde Chen, Zhongfeng Cui, Xiaojiu Cao, Jing Su, Guangming Li

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Article in European journal of medical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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7 authors.

Hongzhi LiDepartment of Tuberculosis Diseases, The Sixth People's Hospital of Zhengzhou, Zhengzhou, 450000, Henan, China. lihongzhi9908@163.com.
Xian GaoDepartment of Tuberculosis Diseases, The Sixth People's Hospital of Zhengzhou, Zhengzhou, 450000, Henan, China.
Chengde ChenDepartment of Tuberculosis Diseases, The Sixth People's Hospital of Zhengzhou, Zhengzhou, 450000, Henan, China.
Zhongfeng CuiDepartment of Clinical Laboratory, The Sixth People's Hospital of Zhengzhou, Zhengzhou, 450000, Henan, China.
Xiaojiu CaoDepartment of Tuberculosis Diseases, The Sixth People's Hospital of Zhengzhou, Zhengzhou, 450000, Henan, China.
Jing SuDepartment of Tuberculosis Diseases, The Sixth People's Hospital of Zhengzhou, Zhengzhou, 450000, Henan, China.
Guangming LiDepartment of Infectious Diseases and Hepatology, The Sixth People's Hospital of Zhengzhou, Zhengzhou, 450000, Henan, China. lgm177@sina.com.

Funding

Special Project on Traditional Chinese Medicine Research in Henan Province 2024ZY2171the Science and Technology Research Program of Henan Province 252102310236
6 · The paper itself

Abstract

backgroundLung 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.

methodsIn 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.

resultsWe 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.

conclusionsThis 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.

Indexed as

Adenocarcinoma of LungBiomarkers, TumorLung NeoplasmsTumor MicroenvironmentGene Expression ProfilingGene Expression Regulation, NeoplasticHumansPrognosisTranscriptomeBiomarkers, TumorBiomarkersImmune checkpointsImmunityLung adenocarcinomaMolecular subtypeRiskScore

Identifiers

PMID41310864
PMCPMC12752188

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