Pang Xiaoxia, Chen Xinghong, Jing Yuxin, Shi Feng, Chen Xiaoying, Huang Huatuo, Liu Chunhong
Center for Medical Laboratory Science, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi of Guangxi Higher Education Institutions, Baise, China.
Front Immunol. 2025 Jun 12;16:1600713. doi: 10.3389/fimmu.2025.1600713. eCollection 2025.
INTRODUCTION: Acquired Immune Deficiency Syndrome (AIDS) is a chronic and life-threatening condition caused by the human immunodeficiency virus (HIV), which severely weakens the immune system. Despite advances in treatment, AIDS remains incurable. Understanding the molecular mechanisms underlying AIDS progression is crucial for developing effective therapeutic strategies. Therefore, this study aims to identify hub genes associated with AIDS susceptibility and progression, as well as to elucidate potential molecular mechanisms involved. METHODS: We used the Gene Expression Omnibus (GEO) dataset GSE76246 for this study. Differentially expressed genes (DEGs) were screened, and Weighted Gene Co-expression Network Analysis (WGCNA) was employed to construct gene modules associated with HIV infection. Hub genes were identified using the CytoHubba plugin, and their expression profiles were assessed using box plots. The diagnostic potential of these genes was evaluated using receiver operating characteristic (ROC) analysis. Functional enrichment and Gene Set Enrichment Analysis (GSEA) were conducted to identify key biological pathways. Additionally, we analyzed immune cell infiltration and constructed drug-gene interaction, miRNA and transcription factor (TF) regulatory networks. RESULTS: 101 intersection genes were identified by combining DEGs, Oxidative stress genes and module genes from WGCNA. Functional enrichment analysis highlighted key pathways, including oxidative stress response and apoptotic signaling. A protein-protein interaction (PPI) network analysis identified 10 hub genes (TP53, AKT1, JUN, CTNNB1, PXDN, MAPK3, FOS, MMP9, FOXO1, STAT1), which showed strong diagnostic potential, as evidenced by ROC curve analysis. Immune infiltration analysis revealed significant associations between hub genes and various immune cell populations. Furthermore, drug-gene interaction analysis predicted several potential therapeutic compounds. Additionally, miRNA and TF regulatory networks were constructed, identifying critical regulatory elements influencing the expression of hub genes. CONCLUSION: This study identified ten hub genes (TP53, AKT1, JUN, CTNNB1, PXDN, MAPK3, FOS, MMP9, FOXO1, STAT1) that play crucial roles in HIV infection and progression. These genes serve as potential biomarkers for HIV diagnosis and therapeutic targets.
引言:获得性免疫缺陷综合征(AIDS)是一种由人类免疫缺陷病毒(HIV)引起的慢性且危及生命的疾病,它会严重削弱免疫系统。尽管治疗取得了进展,但艾滋病仍然无法治愈。了解艾滋病进展背后的分子机制对于制定有效的治疗策略至关重要。因此,本研究旨在确定与艾滋病易感性和进展相关的枢纽基因,并阐明其中涉及的潜在分子机制。 方法:我们在本研究中使用了基因表达综合数据库(GEO)中的GSE76246数据集。筛选差异表达基因(DEGs),并采用加权基因共表达网络分析(WGCNA)构建与HIV感染相关的基因模块。使用CytoHubba插件识别枢纽基因,并使用箱线图评估其表达谱。使用受试者工作特征(ROC)分析评估这些基因的诊断潜力。进行功能富集和基因集富集分析(GSEA)以确定关键生物学途径。此外,我们分析了免疫细胞浸润并构建了药物 - 基因相互作用、miRNA和转录因子(TF)调控网络。 结果:通过整合DEGs、氧化应激基因和来自WGCNA的模块基因,确定了101个交集基因。功能富集分析突出了关键途径,包括氧化应激反应和凋亡信号传导。蛋白质 - 蛋白质相互作用(PPI)网络分析确定了10个枢纽基因(TP53、AKT1、JUN、CTNNB1、PXDN、MAPK3、FOS、MMP9、FOXO1、STAT1),ROC曲线分析表明它们具有很强的诊断潜力。免疫浸润分析揭示了枢纽基因与各种免疫细胞群体之间的显著关联。此外,药物 - 基因相互作用分析预测了几种潜在的治疗化合物。此外,构建了miRNA和TF调控网络,确定了影响枢纽基因表达的关键调控元件。 结论:本研究确定了十个在HIV感染和进展中起关键作用的枢纽基因(TP53、AKT1、JUN、CTNNB1、PXDN、MAPK3、FOS、MMP9、FOXO1、STAT1)。这些基因可作为HIV诊断的潜在生物标志物和治疗靶点。
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