Department of Emergency Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Trauma Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Comput Math Methods Med. 2023 Feb 8;2023:8072369. doi: 10.1155/2023/8072369. eCollection 2023.
Acute type A aortic dissection (AAD) is a catastrophic disease with high mortality, but the pathogenesis has not been fully elucidated. This study is aimed at identifying hub genes and immune cells associated with the pathogenesis of AAD.
The datasets were downloaded from Gene Expression Omnibus (GEO). Gene Set Enrichment Analysis (GSEA), gene set variation analysis (GSVA), and differential analysis were performed. The differentially expressed genes (DEGs) were intersected with specific genes collected from MSigDB. The gene function and pathway enrichment analysis were also performed on intersecting genes. The key modules were selected by weighted gene coexpression network analysis (WGCNA). Hub genes were identified by least absolute shrinkage and selection operator (LASSO) analysis and were verified in the metadataset. The immune cell infiltration was analyzed by CIBERSORT, and the relationship between hub genes and immune cells was performed by Pearson's correlation analysis. The single-cell RNA sequencing (scRNA-seq) dataset was used to verify the differences in DNA damage and repair signaling pathways and hub genes in different cell types.
The results of GSEA and GSVA indicated that DNA damage and repair processes were activated in the occurrence of AAD. The gene function and pathway enrichment analysis on differentially expressed DNA damage- and repair-related genes showed that these genes were mainly involved in the regulation of the cell cycle process, cellular response to DNA damage stimulus, response to wounding, p53 signaling pathway, and cellular senescence. Three key modules were identified by WGCNA. Five genes were screened as hub genes, including CDK2, EIF4A1, GLRX, NNMT, and SLCO2A1. Naive B cells and Gamma delta T cells ( T cells) were decreased in AAD, but monocytes and M0 macrophages were increased. scRNA-seq analysis included that DNA damage and repair processes were activated in smooth muscle cells (SMCs), tissue stem cells, and monocytes in the aortic wall of patients with AAD.
Our results suggested that DNA damage- and repair-related genes may be involved in the occurrence of AAD by regulating many biological processes. The hub genes and immune cells reported in this study also increase the understanding of AAD.
急性 A 型主动脉夹层（AAD）是一种死亡率很高的灾难性疾病，但发病机制尚未完全阐明。本研究旨在确定与 AAD 发病机制相关的枢纽基因和免疫细胞。
从基因表达综合数据库（GEO）下载数据集。进行基因集富集分析（GSEA）、基因集变异分析（GSVA）和差异分析。将差异表达基因（DEGs）与从 MSigDB 收集的特定基因进行交集。还对交集基因进行基因功能和通路富集分析。通过加权基因共表达网络分析（WGCNA）选择关键模块。通过最小绝对值收缩和选择算子（LASSO）分析确定枢纽基因，并在元数据集进行验证。通过 CIBERSORT 分析免疫细胞浸润，并通过 Pearson 相关分析分析枢纽基因与免疫细胞的关系。使用单细胞 RNA 测序（scRNA-seq）数据集验证不同细胞类型中 DNA 损伤和修复信号通路及枢纽基因的差异。
GSEA 和 GSVA 的结果表明，在 AAD 的发生中，DNA 损伤和修复过程被激活。差异表达的 DNA 损伤和修复相关基因的基因功能和通路富集分析表明，这些基因主要参与细胞周期过程的调节、细胞对 DNA 损伤刺激的反应、对创伤的反应、p53 信号通路和细胞衰老。WGCNA 确定了三个关键模块。筛选出 5 个基因作为枢纽基因，包括 CDK2、EIF4A1、GLRX、NNMT 和 SLCO2A1。AAD 患者主动脉壁中的幼稚 B 细胞和γδ T 细胞（T 细胞）减少，但单核细胞和 M0 巨噬细胞增加。scRNA-seq 分析表明，在 AAD 患者的平滑肌细胞（SMC）、组织干细胞和单核细胞中，DNA 损伤和修复过程被激活。
我们的研究结果表明，通过调节许多生物学过程，DNA 损伤和修复相关基因可能参与 AAD 的发生。本研究报道的枢纽基因和免疫细胞也增加了对 AAD 的理解。
