Background. Acute type A aortic dissection (ATAAD) is one of the most lethal cardiovascular diseases, and its molecular mechanism remains unclear. Methods. 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. Results. 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. Conclusion. 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.

中文翻译：

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急性 A 型主动脉夹层分子调控特征和标志物的鉴定


背景。急性A型主动脉夹层（ATAAD）是最致命的心血管疾病之一，其分子机制尚不清楚。方法。通过 limma R 包分别在 GSE52093、GSE153434、GSE98770 和 GSE84827 中检测到 ATAAD 和对照之间的差异表达基因 (DEG)。 DEG 的共表达网络由 WGCNA 包识别。使用 clusterProfiler R 包对与 ATAAD 正相关的模块基因进行富集分析。此外，ChAMP 包还鉴定了主动脉夹层和对照之间的差异甲基化标记物。与ATAAD相关基因进行比较后，基于STRING数据库建立了蛋白质-蛋白质相互作用（PPI）网络。具有最高连通性的基因被确定为中心基因。最后，通过 ssGSEA 鉴定了 ATAAD 和对照之间的差异免疫细胞浸润。结果。从GSE52093和GSE153434中获得268个模块基因，差异表达方向一致，与ATAAD高度相关。它们在 T 细胞激活、HIF-1 信号通路和细胞周期方面显着富集。此外，从GSE84827中获得了2060个差异甲基化标记。其中，77个甲基化标记为ATAAD相关DEG。使用 PPI 网络，我们确定 MYC、ITGA2、RND3、BCL2 和 PHLPP2 作为中心基因。最后，我们在 ATAAD 中鉴定出显着差异浸润的免疫细胞。结论。我们确定的中心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 的发展。 这些发现可能为 ATAAD 的分子机制和治疗靶点提供新的见解。