{
  "abstract": "Background Lung adenocarcinoma (LUAD) is a common subtype of non-small cell lung cancer (NSCLC), marked by high incidence and poor prognosis. Although treatments like anti- programmed cell death protein 1 (PD1) therapy or targeted chemotherapy with epidermal growth factor receptor (EGFR) inhibitors have shown remarkable efficacy in LUAD treatment, some patients still do not receive effective treatment.Methods This study combines bioinformatics analysis with experimental validation, integrating genome-wide association studies (GWAS) data from the FinnGen database, IEU OpenGWAS database, and GWAS Catalog database, along with single-cell transcriptomics and spatial transcriptomics data from the Gene Expression Omnibus (GEO) database, to analyze genetic variations and potential pathogenic mechanisms in LUAD. Through GWAS data, we analyzed new SNP loci, risk factors, linkage disequilibrium score (LD Score), and SMR analysis. With an SMR p-value > 0.05 as the filtering threshold, we identified a novel apoptosis-related locus, Serine/Threonine Kinase 24 (STK24). Using single-cell data, we identified the role of STK24-expressing positive cells (STK24posEpi) in the tumor microenvironment.Results Our research found that the apoptosis-related gene STK24 identified by genome-wide association studies is a risk factor for LUAD. STK24posEpi has strong cell communication interactions with fibroblasts, endothelial cells, and others in the tumor microenvironment, mainly through the Macrophage migration inhibitory factor (MIF) and platelet-derived growth factor (PDGF) pathways. STK24posEpi primarily depends on tumor characteristics such as cell apoptosis, metastasis, DNA repair, and differentiation. STK24posEpi exhibits strong tumor stemness characteristics and is located at the origin in the cell developmental trajectory. In the bulk transcriptome cohort, it was found that STK24posEpi is associated with poor prognosis in LUAD patients and a decrease in tumor-associated lymphocyte infiltration. The deep learning prognosis model developed based on STK24posEpi marker genes shows high accuracy in predicting patient prognosis and immune therapy response. Laboratory experiments have shown that STK24 promotes LUAD cell growth and proliferation while inhibiting cell apoptosis ( figure 1).Conclusions The study identified STK24, an apoptosis-related gene, as a risk factor for LUAD and found that STK24-positive epithelial cells communicate with fibroblasts through pathways such as PDGF and MIF. Experimental results indicate that STK24 promotes LUAD cell proliferation and inhibits apoptosis, highlighting its critical role in tumor progression. These findings provide new insights into potential therapeutic targets for LUAD and underscore the importance of understanding STK24-related mechanisms for the development of personalized therapies.Abstract 1273 Figure 1",
  "authors": [
    {
      "affiliations": [
        "The First Affiliated Hospital of Xi’an Jiaotong University, Shanghai, China"
      ],
      "name": "Meng Hou"
    },
    {
      "affiliations": [
        "Shanghai Jiaotong University, Shanghai, China"
      ],
      "name": "Wenzheng Xia"
    }
  ],
  "title": "1273 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",
  "uid": "e8ff8905-49f1-5336-a277-74381ff6995c"
}