肿瘤微环境免疫细胞浸润在肺腺癌进展中的作用机制研究

Mechanism Analysis of Tumor Microenvironment Immune Cell Infiltration Mediated by STRAP in the Progression of Lung Adenocarcinoma

目的通过生物信息学技术,筛选出与肺腺癌(LUAD)复发相关的关键基因和信号通路,为探讨LUAD复发的分子机制提供理论支持。方法从TCGA和GEO数据库中下载LUAD相关数据集,利用加权基因共表达网络分析(WGCNA)算法挑选关键基因模块,采用LASSO-Cox回归分析构建预后模型;Limma算法筛选差异表达基因;Estimate和MCP算法评估免疫细胞浸润。结果共筛选出29个相关基因模块。单因素Cox分析结果显示,仅有4个基因与患者预后显著相关。基于该基因集进行的LASSO-Cox预后模型显示,风险评分高的患者其预后差,提示该模型具有良好的预测能力。该模型筛选出4个关键基因,分别为丝氨酸-苏氨酸激酶受体相关蛋白(STRAP)、G蛋白亚基γ12(GNG 12)、线粒体甘油-3-磷酸酰基转移酶(GPAM)、锚蛋白重复和泛素结构域蛋白1(ANKUB 1)。本研究对STRAP进行了深入分析,结果显示,STRAP在泛癌中呈现广泛高表达,且与多种肿瘤的不良预后及临床病理特征显著相关。STRAP与免疫抑制分子的表达呈显著正相关。高表达STRAP的患者其微环境CD8+T细胞、NK细胞等多种免疫细胞浸润降低,抑癌基因的单核苷酸多态性(SNP)显著升高,呈现“冷肿瘤”表型。此外,免疫组织化学表明,STRAP在肿瘤组织中显著高表达。结论基因模型能够较好地预测患者复发风险,其中STRAP在LUAD发展中可能发挥重要作用。

Objective To identify the key genes and signaling pathways associated with the recurrence of lung adenocarcinoma(LUAD)by bioinformatics technology,so as to provide theoretical support for exploring the molecular mechanism of the recurrence of LUAD.Methods LUAD related datasets were downloaded from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.The weighted gene co-expression network analysis(WGCNA)algorithm was used to select key module genes.LASSO-Cox regression analysis was employed to construct a prognostic model.The differential gene expression was screened using the Limma algorithm.And the immune cell infiltration was evaluated using Estimate and MCP algorithms.Results A total of 29 related gene modules were identified.Univariate Cox analysis revealed that only 4 genes were significantly associated with the prognosis of patients.The LASSO-Cox prognostic model based on this gene set demonstrated poor prognosis in patients with high risk scores,suggesting good predictive capability of the model.The model identified 4 key genes:serine-threonine kinase receptor-associated protein(STRAP),G-protein gamma-12 subunit(GNG 12),glycerol-3-phosphate acyltransferases mitochondrial(GPAM),and ankyrin repeat and IBR domain-containing protein 1(ANKUB 1).Subsequent in-depth analysis of STRAP showed widespread high expression across various cancers,and significant correlation with poor prognosis and clinical-pathological features.STRAP expression was positively correlated with the expression of immune checkpoint molecules.Patients with high STRAP expression exhibited reduced infiltration of immune cells such as CD8+T cells and NK cells in the tumor microenvironment,along with significantly elevated single nucleotide polymorphisms(SNPs)in tumor suppressor genes,indicative of a"cold tumor"phenotype.Additionally,immunohistochemistry confirmed significant upregulation of STRAP in tumor tissues.Conclusion The gene model effectively predicts the recurrence risk of LUAD in patients,highlighting the potential critical role of STRAP in the development of LUAD.