Yang Qichong, Liu Juncheng, Zhang Tingting, Zhu Tingting, Yao Siyu, Wang Rongzi, Wang Wenjuan, Dilimulati Haliminai, Ge Junbo, An Songtao
Central China Fuwai Hospital of Zhengzhou University, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan, China.
Key Laboratory of Cardiac Regenerative Medicine, National Health Commission, Central China Subcenter of National Center for Cardiovascular Diseases, Henan Cardiovascular Disease Center, Zhengzhou, Henan, China.
Front Mol Neurosci. 2024 Oct 8;17:1477903. doi: 10.3389/fnmol.2024.1477903. eCollection 2024.
Insomnia (ISM) is one of the non-traditional drivers of atherosclerosis (AS) and an important risk factor for AS-related cardiovascular disease. Our study aimed to explore the shared pathways and diagnostic biomarkers of ISM-related AS using integrated bioinformatics analysis.
We download the datasets from the Gene Expression Omnibus database and the GeneCards database. Weighted gene co-expression network analysis and gene differential expression analysis were applied to screen the AS-related gene set. The shared genes of ISM and AS were obtained by intersecting with ISM-related genes. Subsequently, candidate diagnostic biomarkers were identified by constructing protein-protein interaction networks and machine learning algorithms, and a nomogram was constructed. Moreover, to explore potential mechanisms, a comprehensive analysis of shared genes was carried out, including enrichment analysis, protein interactions, immune cell infiltration, and single-cell sequencing analysis.
We successfully screened 61 genes shared by ISM and AS, of which 3 genes (, , and ) were identified as diagnostic biomarkers. A nomogram with excellent predictive value was constructed (the area under curve of the model constructed by the biomarkers was 0.931, and the validation set was 0.745). In addition, the shared genes were mainly enriched in immune and inflammatory response regulation pathways. The biomarkers were associated with a variety of immune cells, especially myeloid immune cells.
We constructed a diagnostic nomogram based on , , and and explored the inflammatory-immune mechanisms, which indicated new insights for early diagnosis and treatment of ISM-related AS.
失眠(ISM)是动脉粥样硬化(AS)的非传统驱动因素之一,也是AS相关心血管疾病的重要危险因素。我们的研究旨在通过综合生物信息学分析探索ISM相关AS的共同途径和诊断生物标志物。
我们从基因表达综合数据库和基因卡片数据库下载数据集。应用加权基因共表达网络分析和基因差异表达分析来筛选AS相关基因集。通过与ISM相关基因相交获得ISM和AS的共同基因。随后,通过构建蛋白质-蛋白质相互作用网络和机器学习算法鉴定候选诊断生物标志物,并构建列线图。此外,为了探索潜在机制,对共同基因进行了全面分析,包括富集分析、蛋白质相互作用、免疫细胞浸润和单细胞测序分析。
我们成功筛选出61个ISM和AS共有的基因,其中3个基因(、和)被鉴定为诊断生物标志物。构建了具有优异预测价值的列线图(由生物标志物构建的模型的曲线下面积为0.931,验证集为0.745)。此外,共同基因主要富集于免疫和炎症反应调节途径。生物标志物与多种免疫细胞相关,尤其是髓系免疫细胞。
我们基于、和构建了诊断列线图并探索了炎症-免疫机制,这为ISM相关AS的早期诊断和治疗提供了新的见解。