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机器学习识别出与阻塞性睡眠呼吸暂停中铁死亡相关的潜在诊断生物标志物。

Machine learning identifies potential diagnostic biomarkers associated with ferroptosis in obstructive sleep apnea.

作者信息

Chen Bowen, Dong Liping, Chi Weiwei, Song Dongmei

机构信息

Clinical Biobank, The First Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang, Hebei 050031, P.R. China.

出版信息

Exp Ther Med. 2025 Mar 13;29(5):95. doi: 10.3892/etm.2025.12845. eCollection 2025 May.

Abstract

Obstructive sleep apnea (OSA) is the most common sleep apnea-related disorder, with a high prevalence and a range of associated complications. Ferroptosis is a new mode of cell death that is involved in the development of OSA, but the mechanism has remained elusive. In the present study, ferroptosis-related genes in OSA were assessed and their potential clinical value was discussed. Data were downloaded and merged, and screened for differentially expressed genes (DEGs) through the Gene Expression Omnibus database. The OSA ferroptosis-related genes were obtained after intersecting with the downloaded ferroptosis-related genes. Subsequently, key ferroptosis-associated differential genes were obtained using two machine learning methods (the least absolute shrinkage and selection operators and random forest). The immune infiltration in the samples and the correlation between key differential genes and immune infiltrating cells were then analyzed. A competing endogenous (ce)RNA visualization network was constructed to find possible therapeutic targets. Finally, the expression levels of key DEGs were verified by reverse transcription-quantitative (RT-q)PCR. In this study, 3 key ferroptosis-related differential genes were identified: TXN, EGR1 and CDKN1A. Functional enrichment analysis showed that the three key differential genes in OSA can influence the development of OSA by affecting metabolism, immune response and other processes. RT-qPCR experiments verified the expression of these key genes, further confirming the findings. A persistent state of immune activation may promote the progression of OSA, with marked infiltration of T cells and natural killer cells in OSA tissues. Genipin is a possible targeted therapeutic agent for OSA. Meanwhile, ceRNA network analysis identified several long non-coding RNAs that can regulate OSA disease progression. A total of 3 key ferroptosis-related markers were identified (TXN, EGR1 and CDKN1A) that are closely associated with metabolic disorders and immune responses, and which may be targets for early diagnosis and treatment of OSA.

摘要

阻塞性睡眠呼吸暂停(OSA)是最常见的与睡眠呼吸暂停相关的疾病,具有高患病率和一系列相关并发症。铁死亡是一种新的细胞死亡模式,参与了OSA的发展,但其机制仍不清楚。在本研究中,评估了OSA中与铁死亡相关的基因,并讨论了它们潜在的临床价值。下载并合并数据,通过基因表达综合数据库筛选差异表达基因(DEGs)。与下载的铁死亡相关基因进行交叉后获得OSA铁死亡相关基因。随后,使用两种机器学习方法(最小绝对收缩和选择算子以及随机森林)获得关键的铁死亡相关差异基因。然后分析样本中的免疫浸润以及关键差异基因与免疫浸润细胞之间的相关性。构建竞争性内源性(ce)RNA可视化网络以寻找可能的治疗靶点。最后,通过逆转录定量(RT-q)PCR验证关键DEGs的表达水平。在本研究中,鉴定出3个关键的铁死亡相关差异基因:TXN、EGR1和CDKN1A。功能富集分析表明,OSA中的这三个关键差异基因可通过影响代谢、免疫反应等过程来影响OSA的发展。RT-qPCR实验验证了这些关键基因的表达,进一步证实了研究结果。免疫激活的持续状态可能促进OSA的进展,OSA组织中有明显的T细胞和自然杀伤细胞浸润。京尼平是一种可能用于OSA的靶向治疗药物。同时,ceRNA网络分析鉴定出几种可调节OSA疾病进展的长链非编码RNA。共鉴定出3个与代谢紊乱和免疫反应密切相关的关键铁死亡相关标志物(TXN、EGR1和CDKN1A),它们可能是OSA早期诊断和治疗的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a89/11947867/04d5a6537c58/etm-29-05-12845-g00.jpg

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