Graduate School of Peking Union Medical College, Beijing, China.
Emergency Department, China-Japan Friendship Hospital, Beijing, China.
Comput Math Methods Med. 2021 Apr 12;2021:6697848. doi: 10.1155/2021/6697848. eCollection 2021.
Acute type A aortic dissection (ATAAD) is one of the most lethal cardiovascular diseases, and its molecular mechanism remains unclear.
Differentially expressed genes (DEGs) between ATAAD and control were detected by limma R package in GSE52093, GSE153434, GSE98770, and GSE84827, respectively. The coexpression network of DEGs was identified by the WGCNA package. Enrichment analysis was performed for module genes that were positively correlated with ATAAD using clusterProfiler R package. In addition, differentially methylated markers between aortic dissection and control were identified by ChAMP package. After comparing with ATAAD-related genes, a protein-protein interaction (PPI) network was established based on the STRING database. The genes with the highest connectivity were identified as hub genes. Finally, differential immune cell infiltration between ATAAD and control was identified by ssGSEA.
From GSE52093 and GSE153434, 268 module genes were obtained with consistent direction of differential expression and high correlation with ATAAD. They were significantly enriched in T cell activation, HIF-1 signaling pathway, and cell cycle. In addition, 2060 differentially methylated markers were obtained from GSE84827. Among them, 77 methylation markers were ATAAD-related DEGs. Using the PPI network, we identified MYC, ITGA2, RND3, BCL2, and PHLPP2 as hub genes. Finally, we identified significantly differentially infiltrated immune cells in ATAAD.
The hub genes we identified may be regulated by methylation and participate in the development of ATAAD through immune inflammation and oxidative stress response. The findings may provide new insights into the molecular mechanisms and therapeutic targets for ATAAD.
急性 A 型主动脉夹层（ATAAD）是最致命的心血管疾病之一，但其分子机制尚不清楚。
分别使用 limma R 包在 GSE52093、GSE153434、GSE98770 和 GSE84827 中检测 ATAAD 和对照之间的差异表达基因（DEGs）。使用 WGCNA 包识别 DEGs 的共表达网络。使用 clusterProfiler R 包对与 ATAAD 呈正相关的模块基因进行富集分析。此外，使用 ChAMP 包鉴定主动脉夹层和对照之间的差异甲基化标记物。在与 ATAAD 相关基因进行比较后，基于 STRING 数据库建立蛋白质-蛋白质相互作用（PPI）网络。鉴定具有最高连通性的基因作为枢纽基因。最后，通过 ssGSEA 鉴定 ATAAD 和对照之间的差异免疫细胞浸润。
从 GSE52093 和 GSE153434 中获得了 268 个模块基因，它们具有一致的差异表达方向和与 ATAAD 高度相关。它们显著富集于 T 细胞激活、HIF-1 信号通路和细胞周期。此外，从 GSE84827 中获得了 2060 个差异甲基化标记物。其中，77 个甲基化标记物是 ATAAD 相关的 DEGs。使用 PPI 网络，我们鉴定出 MYC、ITGA2、RND3、BCL2 和 PHLPP2 作为枢纽基因。最后，我们鉴定出 ATAAD 中显著差异浸润的免疫细胞。
我们鉴定的枢纽基因可能受到甲基化的调节，并通过免疫炎症和氧化应激反应参与 ATAAD 的发生。这些发现可能为 ATAAD 的分子机制和治疗靶点提供新的见解。
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