Evidence map›Paper›PMID 41168822›Full record

ArticleJournal of translational medicine2025

Genome-wide association, single-cell, and spatial transcriptomics analyses reveal the role of the STK24-expressing positive cells in LUAD progression and the tumor microenvironment, identifying STK24 as a potential therapeutic target.

Junzhi Liu, Huimin Li, Yuheng Jiao, Meng Hou

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Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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3 · Its place in the literature

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2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

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4 authors.

Junzhi Liu *Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China. junzhil97@163.com.ORCID 0009-0008-9860-6890
Huimin Li *Internal Medicine Residency Training Base, Gongli Hospital of Shanghai Pudong New Area, Shanghai, 200135, China.
Yuheng JiaoDepartment of Heart Failure, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Meng HouDepartment of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China. houmengdr@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLung adenocarcinoma (LUAD), a subtype of non-small cell lung cancer (NSCLC), has high incidence and poor prognosis. Although anti-programmed cell death protein 1 (PD1) therapy and epidermal growth factor receptor (EGFR) inhibitors benefit some patients, many remain unresponsive. Genome-wide association studies (GWAS) can identify risk loci, while single-cell transcriptomics enables exploration of genetic variations and mechanisms in LUAD.

methodsWe integrated GWAS data from FinnGen, IEU OpenGWAS, and GWAS Catalog with single-cell and spatial transcriptomics from GEO to investigate LUAD genetics and pathology. GWAS analyses identified SNP loci, risk factors, LD Score, and SMR results, revealing a novel apoptosis-related locus, Serine/Threonine Kinase 24 (STK24) (SMR P < 0.05). Single-cell analysis identified STK24-positive epithelial cells (STK24posEpi) and their transcription factors (SCENIC), developmental trajectory (Monocle), and tumor microenvironment roles (CellCall). Spatial mapping (RCTD) and trajectory analysis (stlearn) were combined with cell communication (CellChat), spatial signal flow (Commot), and co-localization (Misty). Bayesian deconvolution linked STK24posEpi to TCGA-LUAD bulk transcriptomes, assessing overall survival (OS), immune infiltration, and clinical traits. A prognostic model (STK24SuperPC, mean c-index 0.61) was built using multiple machine learning algorithms to predict survival and immunotherapy response. Laboratory experiments tested STK24's effects on LUAD cell proliferation and apoptosis.

resultsSTK24 was identified as a LUAD risk factor (pSMR < 0.05). STK24posEpi communicated with fibroblasts, endothelial cells, and others via MIF and PDGF pathways, and was associated with apoptosis (Importance > 0.5), metastasis (Importance > 2), DNA repair (Importance > 1), and DNA damage (Importance > 2). Located at the origin of the trajectory, STK24posEpi correlated with poor prognosis (HR > 0, P < 0.05) and reduced lymphocyte infiltration (Pearson's r < 0, P < 0.05). STK24 overexpression enhanced LUAD cell proliferation, migration, and colony formation, while reducing apoptosis, increasing BCL-2 and Caspase-3, and decreasing Cleaved-Caspase-3 expression.

conclusionsSTK24, an apoptosis-related gene, promotes LUAD progression by enhancing proliferation and inhibiting apoptosis, with STK24posEpi interacting in the tumor microenvironment through PDGF and MIF pathways. These findings offer potential therapeutic targets and support personalized LUAD treatment strategies.

Indexed as

Adenocarcinoma of LungDisease ProgressionGene Expression ProfilingGenome-Wide Association StudyLung NeoplasmsMolecular Targeted TherapyProtein Serine-Threonine KinasesSingle-Cell AnalysisTranscriptomeTumor MicroenvironmentAMP-Activated Protein Kinase KinasesGene Expression Regulation, NeoplasticHumansPolymorphism, Single NucleotideAMP-Activated Protein Kinase KinasesProtein Serine-Threonine KinasesBayesPrismBiomarkerCell apoptosisSingle-cell RNA sequencingSpatial transcriptomicsSTK24

Identifiers

PMID41168822
PMCPMC12574022

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.