基于铁死亡相关基因构建和验证冠心病分子亚型。
Construction and validation of molecular subtypes of coronary artery disease based on ferroptosis-related genes.
机构信息
Department of Cardiology, The Third Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Heping Road, Linghe District, Jinzhou, 121000, Liaoning, China.
出版信息
BMC Cardiovasc Disord. 2022 Jun 22;22(1):283. doi: 10.1186/s12872-022-02719-1.
BACKGROUND
This study aims to construct a reliable diagnostic model for coronary artery disease (CAD) patients and explore its potential mechanism by consensus molecular subtypes of ferroptosis-related genes.
METHODS
GSE12288 and GSE20680 were downloaded from Gene Expression Omnibus database. CAD patients were divided into different molecular subtypes according to the expression level of ferroptosis-related genes. Then, the distribution of differentially expressed genes, functional annotations and immune infiltration cells between the two subtypes were compared. Finally, a prognostic model of ferroptosis-related genes in CAD was constructed and verified.
RESULTS
Two different molecular subtypes of CAD were obtained according to the expression level of ferroptosis-related genes. Then, a total of 1944 differentially expressed genes (DEGs) were found, among which, 236 genes were up-regulated and 1708 genes were down-regulated. In addition, 43 DEGs were ferroptosis-related genes. Functional enrichment analysis showed that these DEGs between two subtypes of CAD were mainly enriched in immune-related pathways and processes, such as T cell receptor, mTOR, NOD-like receptor and Toll-like receptor signaling pathways. We also found that 21 immune cells were significantly changed between two subtypes of CAD. The LASSO method was performed to identify and construct the 16 ferroptosis-related genes-based diagnostic signature. Diagnostic efficiency of diagnostic signature measured by AUC in the training set and validation cohort was 0.971 and 0.899, respectively.
CONCLUSIONS
This study contributes to a more comprehensive understanding of the mechanism of ferroptosis-related genes in CAD.
背景
本研究旨在通过共识的铁死亡相关基因分子亚型构建一个用于诊断冠心病（CAD）患者的可靠模型，并探索其潜在机制。
方法
从基因表达综合数据库中下载 GSE12288 和 GSE20680。根据铁死亡相关基因的表达水平将 CAD 患者分为不同的分子亚型。然后，比较两种亚型之间差异表达基因、功能注释和免疫浸润细胞的分布。最后，构建并验证 CAD 中与铁死亡相关基因的预后模型。
结果
根据铁死亡相关基因的表达水平，得到两种不同的 CAD 分子亚型。然后，发现了总共 1944 个差异表达基因（DEGs），其中 236 个基因上调，1708 个基因下调。此外，有 43 个 DEGs 是铁死亡相关基因。功能富集分析表明，两种 CAD 亚型之间的这些 DEGs 主要富集在免疫相关途径和过程中，如 T 细胞受体、mTOR、NOD 样受体和 Toll 样受体信号通路。我们还发现，两种 CAD 亚型之间有 21 种免疫细胞发生显著变化。使用 LASSO 方法鉴定和构建了基于 16 个铁死亡相关基因的诊断特征。在训练集和验证队列中，诊断特征的 AUC 测量的诊断效率分别为 0.971 和 0.899。
结论
本研究有助于更全面地了解铁死亡相关基因在 CAD 中的作用机制。
Zotero 插件