鉴定与动脉样硬化中的代谢重编程相关的核心基因和转录因子:一个多omics分析和实验验证方法
Yanhong Liu1, Yirong Ma1, Zhijian Song1
1Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang, China.
Frontiers in molecular biosciences
|March 13, 2026
概括
这项研究确定了四个关键的代谢重编程基因 (LYN,FABP5,MMP9,ANPEP) 作为动脉样硬化 (AS) 的诊断生物标志物. 这些基因对免疫微环境调节至关重要,为AS诊断和治疗提供了新的途径.
科学领域:
- 心血管生物学 心血管生物学
- 代谢性疾病研究研究
- 免疫学 免疫学 免疫学
背景情况:
- 动脉样硬化 (AS) 是一种慢性炎症状况,受到代谢重编程 (MR) 的显著影响.
- 了解核心MR相关基因及其在AS中的功能对于识别诊断和治疗生物标志物至关重要.
- 目前的知识差距需要进一步调查AS病变的MR驱动机制.
研究的目的:
- 识别和描述与动脉样硬化相关的核心代谢重编程相关基因 (MRDEGs).
- 评估已识别的MRDEGs的诊断价值,并开发AS的预测模型.
- 阐明这些基因在调节AS免疫微环境中的作用.
主要方法:
- 对两个AS微阵列数据集 (GSE100927,GSE28829) 的综合分析,以确定差异表达基因 (DEG).
- DEGs与用于识别MRDEGs的代谢重编程基因的交叉点.
- 权重基因共同表达网络分析 (WGCNA) 和机器学习算法用于选枢纽基因,使用外部数据 (GSE43292) 和ROC分析进行验证.
- 使用名录和SHAP分析构建和评估一个多基因诊断模型;进行了GSEA,免疫透和单细胞分析.
- 在ApoE-/-小鼠中进行转录因子 (TF) 预测和实验验证.
主要成果:
- 确定了57个MRDEG,其中四个核心基因 (LYN,FABP5,MMP9,ANPEP) 显示出高诊断价值.
- 开发了一种多基因模型,证明了AS的强有力的临床预测性能.
- GSEA和免疫分析显示,GSEA与免疫-炎症通路和免疫微环境重塑有显著的参与.
- EGR1被确定为一个关键的上游转录因子,在小鼠实验验证实了核心基因和EGR1.1的上调.
结论:
- LYN,FABP5,MMP9和ANPEP被确定为AS中核心MR相关的基因,具有显著的诊断价值.
- 这些基因在调节免疫微环境方面发挥着至关重要的作用,为AS的病原发生提供了新的见解.
- 这些发现支持这些基因作为精确诊断和动脉样硬化向治疗的生物标志物的潜力.
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