通过生物信息学和实验验证鉴定和分析 COPD 中的坏死性凋亡相关基因。
Identification and Analysis of Necroptosis-Related Genes in COPD by Bioinformatics and Experimental Verification.
机构信息
Institute of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Hospital of China Medical University, Shenyang 110001, China.
Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang 110001, China.
出版信息
Biomolecules. 2023 Mar 6;13(3):482. doi: 10.3390/biom13030482.
Chronic obstructive pulmonary disease (COPD) is a heterogeneous and complex progressive inflammatory disease. Necroptosis is a newly identified type of programmed cell death. However, the role of necroptosis in COPD is unclear. This study aimed to identify necroptosis-related genes in COPD and explore the roles of necroptosis and immune infiltration through bioinformatics. The analysis identified 49 differentially expressed necroptosis-related genes that were primarily engaged in inflammatory immune response pathways. The infiltration of CD8+ T cells and M2 macrophages in COPD lung tissue was relatively reduced, whereas that of M0 macrophages was increased. We identified 10 necroptosis-related hub genes significantly associated with infiltrated immune cells. Furthermore, 7 hub genes, CASP8, IL1B, RIPK1, MLKL, XIAP, TNFRSF1A, and CFLAR, were validated using an external dataset and experimental mice. CFLAR was considered to have the best COPD-diagnosing capability. TF and miRNA interactions with common hub genes were identified. Several related potentially therapeutic molecules for COPD were also identified. The present findings suggest that necroptosis occurs in COPD pathogenesis and is correlated with immune cell infiltration, which indicates that necroptosis may participate in the development of COPD by interacting with the immune response.
慢性阻塞性肺疾病（COPD）是一种异质性和复杂的进行性炎症性疾病。细胞坏死性凋亡是一种新发现的程序性细胞死亡类型。然而，细胞坏死性凋亡在 COPD 中的作用尚不清楚。本研究旨在鉴定 COPD 中的细胞坏死性凋亡相关基因，并通过生物信息学方法探讨细胞坏死性凋亡和免疫浸润的作用。分析鉴定出 49 个差异表达的细胞坏死性凋亡相关基因，这些基因主要参与炎症免疫反应途径。COPD 肺组织中 CD8+T 细胞和 M2 巨噬细胞的浸润相对减少，而 M0 巨噬细胞的浸润增加。我们鉴定出 10 个与浸润免疫细胞显著相关的细胞坏死性凋亡相关枢纽基因。此外，使用外部数据集和实验小鼠验证了 7 个枢纽基因（CASP8、IL1B、RIPK1、MLKL、XIAP、TNFRSF1A 和 CFLAR）。CFLAR 被认为具有最佳的 COPD 诊断能力。还鉴定了 TF 和 miRNA 与常见枢纽基因的相互作用。还鉴定了几种与 COPD 相关的潜在治疗分子。本研究结果表明，细胞坏死性凋亡发生在 COPD 的发病机制中，并与免疫细胞浸润相关，这表明细胞坏死性凋亡可能通过与免疫反应相互作用参与 COPD 的发展。
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