原发性免疫性血小板减少症中有丝分裂和铁细胞减少的综合分析和预测模型

IF 5.1 2区 医学 Q1 HEMATOLOGY British Journal of Haematology Pub Date : 2024-04-26 DOI:10.1111/bjh.19489
Jiani Mo, Yong Liu, Wencong Zhang, Liang Li, Lindi Li, Tianwen Li, Jiahua Mo, Yujiang Chen, Liang Liang, Yuming Zhang, Mo Yang
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摘要

原发性免疫性血小板减少症(ITP)与特定的致病机制有关,但人们对其与有丝分裂和铁蛋白沉积的关系知之甚少。本研究旨在确定新的生物标志物,并探索有丝分裂和铁吞噬在ITP发病机制中的作用。研究采用了差异分析、Mfuzz表达模式聚类、机器学习、基因组富集分析、单细胞RNA测序(scRNA-seq)和免疫浸润分析等技术来研究关键基因的分子通路。双样本孟德尔随机化(TSMR)评估了ITP的因果效应。在训练集中发现的关键基因包括 GABARAPL1、S100A8、LIN28A 和 GDF9,这些基因在验证集中显示出诊断潜力。功能分析显示,这些基因参与泛素磷酸化、PPAR 信号通路和 T 细胞分化。免疫浸润分析显示,ITP 中巨噬细胞的增加与关键基因有关。scRNA-seq 显示,ITP 骨髓巨噬细胞中 GABARAPL1 的表达减少。TSMR 将 S100A8 与 ITP 诊断联系起来,其 OR 值为 0.856(95% CI = 0.736-0.997,p = 0.045)。该研究指出,GABARAPL1、S100A8、LIN28A 和 GDF9 这四个中心基因与 ITP 中的有丝分裂和铁变态反应有关。研究认为,GABARAPL1表达的减少可能会扰乱泛素磷酸化和PPAR信号,从而损害有丝分裂和抑制铁变态反应,导致免疫失衡。
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Comprehensive analysis and prediction model of mitophagy and ferroptosis in primary immune thrombocytopenia

Primary immune thrombocytopenia (ITP) is linked to specific pathogenic mechanisms, yet its relationship with mitophagy and ferroptosis is poorly understood. This study aimed to identify new biomarkers and explore the role of mitophagy and ferroptosis in ITP pathogenesis. Techniques such as differential analysis, Mfuzz expression pattern clustering, machine learning, gene set enrichment analysis, single-cell RNA sequencing (scRNA-seq) and immune infiltration analysis were employed to investigate the molecular pathways of pivotal genes. Two-sample Mendelian randomization (TSMR) assessed the causal effects in ITP. Key genes identified in the training set included GABARAPL1, S100A8, LIN28A, and GDF9, which demonstrated diagnostic potential in validation sets. Functional analysis indicated these genes' involvement in ubiquitin phosphorylation, PPAR signalling pathway and T-cell differentiation. Immune infiltration analysis revealed increased macrophage presence in ITP, related to the critical genes. scRNA-seq indicated reduced GABARAPL1 expression in ITP bone marrow macrophages. TSMR linked S100A8 with ITP diagnosis, presenting an OR of 0.856 (95% CI = 0.736–0.997, p = 0.045). The study pinpointed four central genes, GABARAPL1, S100A8, LIN28A, and GDF9, tied to mitophagy and ferroptosis in ITP. It posits that diminished GABARAPL1 expression may disrupts ubiquitin phosphorylation and PPAR signalling, impairing mitophagy and inhibiting ferroptosis, leading to immune imbalance.

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来源期刊
CiteScore
8.60
自引率
4.60%
发文量
565
审稿时长
1 months
期刊介绍: The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor.
期刊最新文献
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