Henan Provincial Engineering Laboratory of Insects Bio-Reactor, Nanyang Normal University, Nanyang, China.
Henan Provincial Key Laboratory of Stroke Prevention and Treatment. Nanyang central Hospital, Nanyang, China.
Oxid Med Cell Longev. 2023 Jan 5;2023:5199810. doi: 10.1155/2023/5199810. eCollection 2023.
Atrial fibrillation (AF) is a major risk factor for ischemic stroke. We aimed to identify novel potential biomarkers with diagnostic value in patients with atrial fibrillation-related cardioembolic stroke (AF-CE).Publicly available gene expression profiles related to AF, cardioembolic stroke (CE), and large artery atherosclerosis (LAA) were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified and then functionally annotated. The support vector machine recursive feature elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO) regression analysis were conducted to identify potential diagnostic AF-CE biomarkers. Furthermore, the results were validated by using external data sets, and discriminability was measured by the area under the ROC curve (AUC). In order to verify the predictive results, the blood samples of 13 healthy controls, 20 patients with CE, and 20 patients with LAA stroke were acquired for RT-qPCR, and the correlation between biomarkers and clinical features was further explored. Lastly, a nomogram and the companion website were developed to predict the CE-risk rate. Three feature genes (C1QC, VSIG4, and CFD) were selected and validated in the training and the external datasets. The qRT-PCR evaluation showed that the levels of blood biomarkers (C1QC, VSIG4, and CFD) in patients with AF-CE can be used to differentiate patients with AF-CE from normal controls ( < 0.05) and can effectively discriminate AF-CE from LAA stroke ( < 0.05). Immune cell infiltration analysis revealed that three feature genes were correlated with immune system such as neutrophils. Clinical impact curve, calibration curves, ROC, and DCAs of the nomogram indicate that the nomogram had good performance. Our findings showed that C1QC, VSIG4, and CFD can potentially serve as diagnostic blood biomarkers of AF-CE; novel nomogram and the companion website can help clinicians to identify high-risk individuals, thus helping to guide treatment decisions for stroke patients.
心房颤动（AF）是缺血性中风的主要危险因素。我们旨在确定与心房颤动相关的心源性栓塞性中风（AF-CE）患者具有诊断价值的新型潜在生物标志物。从基因表达综合数据库（GEO）中下载与 AF、心源性栓塞（CE）和大动脉粥样硬化（LAA）相关的公开基因表达谱。鉴定差异表达基因（DEGs），然后进行功能注释。采用支持向量机递归特征消除（SVM-RFE）和最小绝对值收缩和选择算子（LASSO）回归分析鉴定潜在的诊断 AF-CE 生物标志物。进一步使用外部数据集验证结果，并通过 ROC 曲线下面积（AUC）衡量可区分性。为了验证预测结果，采集了 13 名健康对照者、20 名 CE 患者和 20 名 LAA 中风患者的血液样本进行 RT-qPCR，并进一步探讨了生物标志物与临床特征之间的相关性。最后，开发了一个列线图和配套网站来预测 CE 风险率。在训练集和外部数据集中选择并验证了三个特征基因（C1QC、VSIG4 和 CFD）。qRT-PCR 评估表明，AF-CE 患者血液生物标志物（C1QC、VSIG4 和 CFD）的水平可用于区分 AF-CE 患者与正常对照者（<0.05），并可有效区分 AF-CE 与 LAA 中风（<0.05）。免疫细胞浸润分析表明，三个特征基因与中性粒细胞等免疫系统相关。列线图的临床影响曲线、校准曲线、ROC 和 DCA 表明该列线图具有良好的性能。我们的研究结果表明，C1QC、VSIG4 和 CFD 可能作为 AF-CE 的诊断性血液生物标志物；新型列线图和配套网站可帮助临床医生识别高危个体，从而有助于指导中风患者的治疗决策。
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