Wang Sixian, Tai Yuxing, Yang Xiaoqian, Li Peizhe, Wang Han, Tan Yi, Gao Tianjiao, Chu Mingrui, Liu Mingjun
Changchun University of Chinese Medicine, Changchun 130117, China.
College of Acupuncture and Massage, Changchun University of Chinese Medicine, Changchun 130117, China.
Heliyon. 2024 Oct 11;10(20):e39039. doi: 10.1016/j.heliyon.2024.e39039. eCollection 2024 Oct 30.
The relationship between COVID-19 and ischemic stroke (IS) has attracted significant attention, yet the precise mechanism at the gene level remains unclear. This study aims to reveal potential biomarkers and drugs for COVID-19-related IS through bioinformatics methods. We collected two gene expression profiling datasets, GSE16561 and GSE213313, and selected GSE179879 and GSE196822 as validation sets for analysis. Through analysis, we identified 77 differentially expressed genes (DEGs) shared between COVID-19 and IS. Further gene enrichment analysis revealed that these genes are primarily involved in immune regulation. By constructing a protein-protein interaction network, we screened out nine hub genes, including FCGR3A, KLRB1, IL2RB, CD2, IL7R, CCR7, CD3D, GZMK, and ITK. In LASSO regression analysis, we evaluated the ROC curve's area under the curve (AUC) scores of key genes to assess their diagnostic accuracy. Subsequently, we performed random forest (RF), Support Vector Machine Recursive Feature Elimination (SVM-RFE), and neural network construction on hub genes to ensure accurate diagnosis of IS. Finally, by intersecting the results of three algorithms (LASSO regression, random forest, and SVM), CD3D and ITK were identified as the ultimate key genes. Based on this, we predicted potential targeted drug Blinatumomab. These research findings provide clues for a deeper understanding of the biological mechanisms of COVID-19-related IS and offer new insights for exploring novel treatment approaches.
新型冠状病毒肺炎(COVID-19)与缺血性脑卒中(IS)之间的关系已引起广泛关注,但其在基因水平的精确机制仍不清楚。本研究旨在通过生物信息学方法揭示与COVID-19相关的IS的潜在生物标志物和药物。我们收集了两个基因表达谱数据集GSE16561和GSE213313,并选择GSE179879和GSE196822作为验证集进行分析。通过分析,我们确定了COVID-19和IS之间共有的77个差异表达基因(DEG)。进一步的基因富集分析表明,这些基因主要参与免疫调节。通过构建蛋白质-蛋白质相互作用网络,我们筛选出9个枢纽基因,包括FCGR3A、KLRB1、IL2RB、CD2、IL7R、CCR7、CD3D、GZMK和ITK。在LASSO回归分析中,我们评估了关键基因的ROC曲线下面积(AUC)得分,以评估其诊断准确性。随后,我们对枢纽基因进行了随机森林(RF)、支持向量机递归特征消除(SVM-RFE)和神经网络构建,以确保对IS的准确诊断。最后,通过交叉三种算法(LASSO回归、随机森林和SVM)的结果,确定CD3D和ITK为最终关键基因。基于此,我们预测了潜在的靶向药物Blinatumomab。这些研究结果为深入了解COVID-19相关IS的生物学机制提供了线索,并为探索新的治疗方法提供了新的见解。