基于双相障碍患者转录组的基因富集及免疫细胞浸润分析
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河北省卫生健康创新专项(21377712D);保定市科技计划项目(2341ZF258)


Transcriptome-based gene enrichment and immune cell infiltration analysis in patients with bipolardisorder
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    摘要:

    目的 探讨双相障碍(BD)患者外周血单个核细胞(PBMC)中mRNA的整体表达情况并进 行免疫浸润分析。方法 选取2022 年10 月—2023 年7 月河北医科大学第一医院精神卫生中心就诊的 24 例BD 患者和12 名健康对照(HC)者为研究对象。使用微阵列分析36 名入组者PBMC 中全基因组基 因表达谱,进行基因本体(GO)和京都基因与基因组百科全书(KEGG)途径富集分析,此外,本研究还进 行了蛋白质-蛋白质相互作用(PPI)分析,并且利用基因集变异分析(GSVA)评估免疫细胞浸润及其相 互关系。结果 在BD 患者与HC 者比较中,共发现304 个差异表达基因(DEGs),其中217 个基因上调, 87 个基因下调。通过富集分析,提示与细胞外基质、应激反应、肝素结合以及免疫炎症等方面相关的 生物过程及信号通路在BD 者中上调;在IL-17 信号通路中,与HC 者相比,BD 患者中Jun、Fosb、Fosl1、 TNFAIP3、NFKBIA、CXCL2、CXCL8、IL6 和IL17C基因表达上调,实时定量反转录PCR(qRT-PCR)分析 结果显示,Jun、Fosb、Fosl1、NFKBIA,TNFAIP3,CXCL2和CXCL8基因表达在BD 中均上调,但只有Jun、 Fosl1、NFKBIA、CXCL2和CXCL8基因表达差异有统计学意义(均P< 0.05)。免疫浸润分析显示,中枢记 忆CD4+ T 细胞(P=0.010)、嗜酸性粒细胞(P=0.038)和肥大细胞(P=0.029)在BD 患者中浸润增加,效应记 忆CD8+ T细胞与活化CD8+ T细胞、T滤泡辅助细胞呈正相关(r=0.56、0.58,均P < 0.05)。结论 本研究 整合了转录组学和免疫微环境分析,揭示BD患者外周免疫系统的特征性变化,提示外周免疫系统可能通过 趋化因子引发的炎症反应参与BD的发病机制。此外,免疫浸润分析显示BD患者存在慢性免疫激活状态。

    Abstract:

    Objective To explore the overall expression of mRNA in peripheral blood mononuclear cell( PBMC) of patients with bipolar disorder( BD) and analyze the immune infiltration. Methods From October 2022 to July 2023, 24 patients with BD and 12 healthy controls( HC) attending the Mental Health Center of the First Hospital of Hebei Medical University were selected for the study. Genome-wide gene expression profiles in PBMC of 36 enrollees were analyzed using microarrays for Gene Ontology( GO) and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment analysis. Protein-protein interaction( PPI) analysis was performed and immune cell infiltration and its interrelationships were assessed using gene set variation analysis( GSVA). Results A total of 304 differentially expressed genes( DEGs) were identified in BD versus HC comparisons, of which 217 genes were upregulated and 87 genes were downregulated. Enrichment analysis suggested that biological processes and signaling pathways related to extracellular matrix, stress response, heparin binding, and immune inflammation were upregulated in BD group. In the IL-17 pathway, Jun, Fosb, Fosl1, TNFAIP3, NFKBIA, CXCL2, CXCL8, IL6, and IL17C gene expression was upregulated in BD patients compared to HC. Real-time quantitative reverse transcription PCR( qRT-PCR) analysis showed that Jun, Fosb, Fosl1, NFKBIA, TNFAIP3, CXCL2 and CXCL8 gene expression were upregulated in BD, but only Jun, Fosl1, NFKBIA, CXCL2 and CXCL8 changes were statistically significant( all P<0.05). Immune infiltration analysis showed that central memory CD4+ T cells( P=0.010), eosinophils( P=0.038) and mast cells( P=0.029) were infiltrated increased in BD group, and there were positive correlations between effector memory CD8+ T cells and activated CD8+ T cells and T follicular helper cells, and the differences were statistically significant( r=0.56,0.58, both P < 0.05). Conclusions This study integrates transcriptomics and immune microenvironment analysis to reveal characteristic changes in the peripheral immune system of BD patients, suggesting that the peripheral immune system may be involved in the pathogenesis of BD through chemokine-induced inflammatory responses. Immune infiltration analysis reveals the presence of a chronic immune activation state in patients with BD.

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王晓博,王育梅,张天乐,谢婷婷,苏昱.基于双相障碍患者转录组的基因富集及免疫细胞浸润分析[J].神经疾病与精神卫生,2025,25(7):465-473
DOI :10.3969/j. issn.1009-6574.2025.07.002.

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  • 在线发布日期: 2025-07-22