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加权基因共表达网络分析和机器学习用于确定胸腺瘤相关重症肌无力中Tfh细胞和B细胞浸润生物标志物

Weighted gene coexpression network analysis and machine learning for the determination of tfh cell and B cell infiltrating biomarkers in thymoma-associated myasthenia gravis.

作者信息

Li Zidong, Miao Lu, Ren Gang, Wang Hailong, Shangguan Lijuan, Zhao Hongping, Li Xinyi

机构信息

Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongiji Shanxi Hospital, Taiyuan, 030032, China.

出版信息

Heliyon. 2024 Jul 10;10(14):e34364. doi: 10.1016/j.heliyon.2024.e34364. eCollection 2024 Jul 30.

Abstract

Patients with thymoma (THYM)-associated myasthenia gravis (MG) typically have a poor prognosis and recurring illness. This study aimed to discover important biomarkers associated with immune cell infiltration and THYM-associated MG (THYM-MG) development. Gene expression microarray data were downloaded from The Cancer Genome Atlas website (TCGA) and Gene Expression Omnibus (GEO). A total of 102 differentially expressed genes were investigated. According to the immune infiltration data, the distribution of Tfh cells, B cells, and CD4 T cells differed significantly between the THYM-MG and THYM-NMG groups. WGCNA derived 25 coexpression modules; one hub module (the blue module) strongly correlated with Tfh cells. Combining differential genes revealed 21 intersecting genes. LASSO analysis subsequently revealed 16 hub genes as potential THYM-MG biomarkers. ROC curve analysis of the predictive model revealed moderate diagnostic value. The association between the 16 hub genes and infiltrating immune cells was further evaluated in TIMER2.0 and the validation dataset. Draggability analysis identified the therapeutic target genes PTGS2 and ALB, along with significant drugs including Firocoxib, Alclofenac, Pyridostigmine, and Stavudine. This was validated through MD simulation, PCA, and MM-GBSA analyses. The interaction between numerous activated B cells and follicular helper T cells is closely associated with THYM-MG pathogenesis from a bioinformatics perspective. Hub genes (including , , , and ) may be downregulated in immune cells in THYM-MG and associated with progression.

摘要

胸腺瘤(THYM)相关重症肌无力(MG)患者通常预后较差且病情易反复。本研究旨在发现与免疫细胞浸润及胸腺瘤相关重症肌无力(THYM-MG)发生发展相关的重要生物标志物。基因表达微阵列数据从癌症基因组图谱网站(TCGA)和基因表达综合数据库(GEO)下载。共研究了102个差异表达基因。根据免疫浸润数据,THYM-MG组和THYM-NMG组之间的滤泡辅助性T细胞、B细胞和CD4 T细胞分布存在显著差异。加权基因共表达网络分析(WGCNA)得出25个共表达模块;一个核心模块(蓝色模块)与滤泡辅助性T细胞高度相关。结合差异基因揭示了21个交集基因。随后的套索分析揭示了16个核心基因作为潜在的THYM-MG生物标志物。预测模型的ROC曲线分析显示出中等诊断价值。在TIMER2.0和验证数据集中进一步评估了这16个核心基因与浸润免疫细胞之间的关联。药物可及性分析确定了治疗靶点基因环氧化酶2(PTGS2)和白蛋白(ALB),以及包括非罗考昔、阿氯芬酸、吡啶斯的明和司他夫定在内的重要药物。通过分子动力学模拟(MD)、主成分分析(PCA)和分子力学/广义玻恩表面面积法(MM-GBSA)分析进行了验证。从生物信息学角度来看,众多活化B细胞与滤泡辅助性T细胞之间的相互作用与THYM-MG发病机制密切相关。核心基因(包括 、 、 和 )在THYM-MG免疫细胞中可能下调并与疾病进展相关。 (注:原文中部分基因名称未给出具体内容,用“ ”表示)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d05/11301372/5324df8f7753/gr1.jpg

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