背景:循环单核细胞的丰度与人类动脉粥样硬化的发展密切相关。
目的:本研究旨在进一步研究颈动脉粥样硬化(CAS)的诊断生物标志物和靶向治疗。
方法:我们在有和没有CAS的公共数据库中,通过加权基因共表达网络分析(WGCNA)对患者的单核细胞进行了转录组学分析。通过R包limma筛选差异表达基因(DEGs)。通过最小绝对收缩和选择算子(LASSO)和支持向量机递归特征消除(SVM-RFE)算法得出诊断分子。NetworkAnalyst,miRWalk,和StarBase数据库协助构建诊断分子调控网络。DrugBank数据库预测了靶向诊断分子的药物。RT-PCR测试表达谱。
结果:来自14,369个hub基因和61个DEG,6个差异表达的单核细胞相关hub基因与免疫细胞显著相关,免疫反应,单核细胞,和脂质代谢。LASSO和SVM-RFE产生了5个用于CAS预测的基因。这些基因的RT-PCR显示HMGB1上调,与对照组相比,CAS中CCL3、CCL3L1、CCL4和DUSP1下调。然后,我们构建并可视化了9种转录因子(TFs)的调控网络,与5种诊断分子显著相关。大约11个miRNAs,19个lncRNAs,构建并展示了以四种诊断分子(CCL3,CCL4,DUSP1和HMGB1)为中心的39条边。确定了11种潜在药物,包括ibrutinib,CTI-01、罗氟司特等.结论:确定了一组用于CAS诊断和潜在治疗靶标研究的五种生物标志物。
BACKGROUND: The abundance of circulating monocytes is closely associated with the development of atherosclerosis in humans.
OBJECTIVE: This study aimed to further research into diagnostic biomarkers and targeted treatment of carotid atherosclerosis (CAS).
METHODS: We performed transcriptomics analysis through weighted gene co-expression network analysis (WGCNA) of monocytes from patients in public databases with and without CAS. Differentially expressed genes (DEGs) were screened by R package limma. Diagnostic molecules were derived by the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) algorithms. NetworkAnalyst, miRWalk, and Star- Base databases assisted in the construction of diagnostic molecule regulatory networks. The Drug- Bank database predicted drugs targeting the diagnostic molecules. RT-PCR tested expression profiles.
RESULTS: From 14,369 hub genes and 61 DEGs, six differentially expressed monocyte-related hub genes were significantly associated with immune cells, immune responses, monocytes, and lipid metabolism. LASSO and SVM-RFE yielded five genes for CAS prediction. RT-PCR of these genes showed HMGB1 was upregulated, and CCL3, CCL3L1, CCL4, and DUSP1 were downregulated in CAS versus controls. Then, we constructed and visualized the regulatory networks of 9 transcription factors (TFs), which significantly related to 5 diagnostic molecules. About 11 miRNAs, 19 lncRNAs, and 39 edges centered on four diagnostic molecules (CCL3, CCL4, DUSP1, and HMGB1) were constructed and displayed. Eleven potential drugs were identified, including ibrutinib, CTI-01, roflumilast etc. Conclusion: A set of five biomarkers were identified for the diagnosis of CAS and for the study of potential therapeutic targets.