Xing Yanqing, Feng Liting, Dong Yangdou, Li Yupeng, Zhang Lulu, Wu Qiannan, Huo Rujie, Dong Yanting, Tian Xinrui, Tian Xinli
Department of Respiratory and Critical Care Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China.
College of Basic Medicine, Shanxi Medical University, Taiyuan, People's Republic of China.
J Asthma Allergy. 2023 Jul 12;16:689-710. doi: 10.2147/JAA.S416276. eCollection 2023.
Asthma is a chronic inflammatory airway disease involving multiple mechanisms, of which ferroptosis is a form of programmed cell death. Recent studies have shown that ferroptosis may play a crucial role in the pathogenesis of asthma, but no specific ferroptosis gene has been found in asthma, and the exact mechanism is still unclear. The present study aimed to screen ferroptosis genes associated with asthma and find therapeutic targets, in order to contribute a new clue for the diagnosis and therapy of asthma.
Ferroptosis-related differentially expressed genes (FR-DEGs) in asthma were selected by the GSE41861, GSE43696 and ferroptosis datasets. Next, the FR-DEGs were subjected by GO and KEGG enrichment, and the mRNA-miRNA network was constructed. Then, GSEA and GSVA enrichment analysis and Immune infiltration analysis were performed, followed by targeted drug prediction. Finally, the expression of FR-DEGs was confirmed using GSE63142 dataset and RT-PCR assay.
We found 13 FR-DEGs by the GSE41861, GSE43696 and ferroptosis database. Functional enrichment analysis revealed that the 13 FR-DEGs were enriched in oxidative stress, immune response, ferroptosis, lysosome, necrosis, apoptosis etc. Moreover, our results revealed the mRNA-miRNA network of the FR-DEGs and identified candidate drugs. Also, immune infiltration revealed that ELAVL1, CREB5, CBR1 and NR1D2 are associated with the immune cells and may be potential targets in asthma. Finally, 10 FR-DEGs were validated by the GSE63142 database. It was verified that 7 FR-DEGs were differentially expressed by collecting asthma patients and healthy controls.
This study ultimately identified 7 FR-DEGs for the diagnosis and therapy of asthma. These 7 FR-DEGs contribute to oxidative stress and immune responses. This study provides potential therapeutic targets and biomarkers for asthma patients, shedding further light on the pathogenesis of asthma as well as providing new insights into the treatment of asthma.
哮喘是一种涉及多种机制的慢性炎症性气道疾病，其中铁死亡是一种程序性细胞死亡形式。近期研究表明，铁死亡可能在哮喘发病机制中起关键作用，但在哮喘中尚未发现特定的铁死亡基因，确切机制仍不清楚。本研究旨在筛选与哮喘相关的铁死亡基因并寻找治疗靶点，为哮喘的诊断和治疗提供新线索。
通过GSE41861、GSE43696和铁死亡数据集选择哮喘中与铁死亡相关的差异表达基因（FR-DEGs）。接下来，对FR-DEGs进行GO和KEGG富集，并构建mRNA-miRNA网络。然后，进行GSEA和GSVA富集分析以及免疫浸润分析，随后进行靶向药物预测。最后，使用GSE63142数据集和RT-PCR检测法确认FR-DEGs的表达。
通过GSE41861、GSE43696和铁死亡数据库，我们发现了13个FR-DEGs。功能富集分析显示，这13个FR-DEGs在氧化应激、免疫反应、铁死亡、溶酶体、坏死、凋亡等方面富集。此外，我们的结果揭示了FR-DEGs的mRNA-miRNA网络并鉴定出候选药物。免疫浸润分析显示，ELAVL1、CREB5、CBR1和NR1D2与免疫细胞相关，可能是哮喘的潜在靶点。最后，10个FR-DEGs通过GSE63142数据库得到验证。通过收集哮喘患者和健康对照，验证了7个FR-DEGs存在差异表达。
本研究最终鉴定出7个用于哮喘诊断和治疗的FR-DEGs。这7个FR-DEGs参与氧化应激和免疫反应。本研究为哮喘患者提供了潜在的治疗靶点和生物标志物，进一步阐明了哮喘的发病机制，并为哮喘治疗提供了新的见解。
