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利用机器学习识别和验证冠状动脉疾病中的免疫原性细胞死亡生物标志物和免疫表型

Use of Machine Learning for the Identification and Validation of Immunogenic Cell Death Biomarkers and Immunophenotypes in Coronary Artery Disease.

作者信息

Zhang Yan-Jiao, Huang Chao, Zu Xiu-Guang, Liu Jin-Ming, Li Yong-Jun

机构信息

Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People's Republic of China.

Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, People's Republic of China.

出版信息

J Inflamm Res. 2024 Jan 12;17:223-249. doi: 10.2147/JIR.S439315. eCollection 2024.

DOI:10.2147/JIR.S439315
PMID:38229693
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10790656/
Abstract

OBJECTIVE

Immunogenic cell death (ICD) is part of the immune system's response to coronary artery disease (CAD). In this study, we bioinformatically evaluated the diagnostic and therapeutic utility of immunogenic cell death-related genes (IRGs) and their relationship with immune infiltration features in CAD.

METHODS

We acquired the CAD-related datasets GSE12288, GSE71226, and GSE120521 from the Gene Expression Omnibus (GEO) database and the IRGs from the GeneCards database. After identifying the immune cell death-related differentially expressed genes (IRDEGs), we developed a risk model and detected immune subtypes in CAD. IRDEGs were identified using least absolute shrinkage and selection operator (LASSO) analysis. Using a nomogram, we confirmed that both the LASSO model and ICD signature genes had good diagnostic performance.

RESULTS

There was a high degree of coincidence and immune representativeness between two CAD groups based on characteristic genes and hub genes. Hub genes were associated with the interaction of neuroactive ligands with receptors and cell adhesion receptors. The two groups differed in terms of adipogenesis, allograft rejection, and apoptosis, as well as the ICD signature and hub gene expression levels. The two CAD-ICD subtypes differed in terms of immune infiltration.

CONCLUSION

Quantitative real-time PCR (qRT-PCR) correlated CAD with the expression of , and . The ICD signature genes are candidate biomarkers and reference standards for immune grouping in CAD and can be beneficial in precise immune-targeted therapy.

摘要

目的

免疫原性细胞死亡（ICD）是免疫系统对冠状动脉疾病（CAD）反应的一部分。在本研究中，我们通过生物信息学方法评估了免疫原性细胞死亡相关基因（IRGs）在CAD中的诊断和治疗效用及其与免疫浸润特征的关系。

方法

我们从基因表达综合数据库（GEO）获取了与CAD相关的数据集GSE12288、GSE71226和GSE120521，并从基因卡片数据库获取了IRGs。在鉴定出免疫细胞死亡相关差异表达基因（IRDEGs）后，我们构建了一个风险模型并检测了CAD中的免疫亚型。使用最小绝对收缩和选择算子（LASSO）分析来鉴定IRDEGs。通过列线图，我们证实LASSO模型和ICD特征基因均具有良好的诊断性能。

结果

基于特征基因和枢纽基因的两个CAD组之间存在高度的一致性和免疫代表性。枢纽基因与神经活性配体与受体以及细胞粘附受体的相互作用相关。两组在脂肪生成、同种异体移植排斥、细胞凋亡以及ICD特征和枢纽基因表达水平方面存在差异。两种CAD-ICD亚型在免疫浸润方面存在差异。

结论

定量实时PCR（qRT-PCR）将CAD与 、 和 的表达相关联。ICD特征基因是CAD免疫分组的候选生物标志物和参考标准，有助于精确的免疫靶向治疗。

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