Department of Cardiac Surgery, The First Affiliated Hospital of Kunming Medical University, Yunnan, China.
School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China.
Aging (Albany NY). 2023 Oct 24;15(20):11268-11285. doi: 10.18632/aging.205126.
Type-A aortic dissection (TAAD) is common life-threatening cardiovascular diseases with high-morbidity and mortality but the concrete etiology of disease remains unclear, which might disturb or delay the early diagnosis for TAAD. Anoikis is a special form of programmed cell-death (PCD) induced by detachment of anchorage-dependent cells from the extracellular matrix (ECM) or neighboring cells, and has been widely applied to identify anoikis-related biomarkers for the prediction and prognosis in oncological fields. However, the specific roles of anoikis-related genes (ARGs) in TAAD remain unclear. In this study, we first identified and validated eight diagnostic ARGs for TAAD based on multiple RNA-sequence datasets, including and The comprehensive functional annotation was evaluated by the integrated functional enrichments analysis. We identified the activation of inflammatory-related pathways, metabolic reprogramming and angiogenesis, and the inhibition of cardiovascular development pathways in TAAD. Immune cell infiltration (ICI) analysis further demonstrated that innate immune-cells were more dominant than adaptive immune-cells in TAAD tissues, especially in macrophages, monocytes, activated-DC, NKT cells and CD56+dim NK cells. The cellular landscape was further validated by single-cell RNA sequence technology with significant associations with anoikis in TAAD patients. Four vital ARGs ( and ) were ultimately identified along with the changes of differentiation trajectory, and major expressions were conformably concentrated on Macro1-3, Mono1-2 and Mono4 subtypes. These findings provide a promising diagnostic biomarker for the accurately diagnosing the disease and would be helpful to further explore the potential pathogenesis with anoikis process for TAAD.
A型主动脉夹层（TAAD）是一种常见的危及生命的心血管疾病，具有高发病率和死亡率，但具体病因仍不清楚，这可能会干扰或延迟 TAAD 的早期诊断。细胞凋亡是锚定依赖性细胞从细胞外基质（ECM）或相邻细胞上脱离而诱导的一种特殊形式的程序性细胞死亡（PCD），已广泛应用于鉴定细胞凋亡相关生物标志物，以预测和评估肿瘤学领域的预后。然而，细胞凋亡相关基因（ARGs）在 TAAD 中的具体作用尚不清楚。在这项研究中，我们首先基于多个 RNA-seq 数据集，包括 TCGA 和 GTEx，鉴定并验证了八个用于 TAAD 的诊断 ARGs。通过整合功能富集分析对其进行了全面的功能注释。我们发现 TAAD 中存在炎症相关途径、代谢重编程和血管生成的激活，以及心血管发育途径的抑制。免疫细胞浸润（ICI）分析进一步表明，在 TAAD 组织中，固有免疫细胞比适应性免疫细胞更为优势，特别是巨噬细胞、单核细胞、激活的 DC、NKT 细胞和 CD56+dim NK 细胞。单细胞 RNA 序列技术进一步验证了细胞景观，与 TAAD 患者的细胞凋亡具有显著相关性。最终确定了四个重要的 ARGs（和），并伴随着分化轨迹的变化，其主要表达集中在 Macro1-3、Mono1-2 和 Mono4 亚型上。这些发现为准确诊断该疾病提供了有前途的诊断生物标志物，并有助于进一步探索与细胞凋亡过程相关的潜在发病机制。
