权重基因共表达网络鉴定外周血脑卒中相关微RNA
| 作者: |
1郑菲菲,
2蒋蔚
1 江南大学附属医院检验科，江苏 无锡 224001 2 南京医科大学附属无锡市第二人民医院神经内科，江苏 无锡 224001 |
| 通讯: |
蒋蔚
Email: jianghaot1986@163.com |
| DOI: | 10.3978/j.issn.2095-6959.2021.12.006 |
摘要
目的：通过分析脑卒中患者外周血微RNA(microRNA，miRNA)表达谱，探索miRNA潜在的诊断价值。方法：下载基因表达综合(Gene Expression Omnibus，GEO)中脑卒中患者和对照组的miRNA表达谱(GSE117064)，使用R软件的“limma”包筛选出具有统计学差异的miRNAs；使用权重基因共表达网络分析(weighted gene co-expression network analysis，WGCNA)识别与脑卒中相关的miRNA；使用Cytoscape软件分析并可视化权重网络；收集脑卒中患者和正常人的外周血miRNA，使用反转录聚合酶链反应(reverse transcription-polymerase chain reaction，RT-PCR)验证；最后，使用R软件的“pROC”包评估枢纽miRNAs诊断脑卒中的价值。结果：通过分析脑卒中患者外周血miRNA芯片数据集，共筛选出641个差异表达miRNAs；WGCNA识别并分析与脑卒中相关的miRNA模块，筛选出4个具有诊断价值的枢纽miRNAs(miR-1910-5p、miR-636、miR-7108-3p和miR-887-3p)；RT-PCR证实miR-1910-5p、miR-636、miR-7108-3p和miR-887-3p在脑卒中患者外周血中表达降低；miR-1910-5p、miR-636、miR-7108-3p和miR-887-3p诊断脑卒中的曲线下面积(area under curve，AUC)依次为0.962、0.970、0.962和0.973；枢纽miRNAs联合诊断脑卒中的AUC为0.987。结论：脑卒中患者外周血异常表达的miRNA是潜在的诊断标志物，为探索脑卒中的发病机制和诊疗策略提供了线索。
关键词：
脑卒中；微RNA；权重基因共表达网络分析；生物标志物
Identification of stroke associated microRNAs in peripheral blood by weighted gene co-expression network analysis
CorrespondingAuthor: JIANG Wei Email: jianghaot1986@163.com
DOI: 10.3978/j.issn.2095-6959.2021.12.006
Abstract
Objective: To explore the molecular mechanism and diagnostic markers of stroke by analyzing the expression profile of peripheral blood microRNA (miRNA). Methods: MiRNA chips of stroke patients and the control group were downloaded from the GEO database (GSE117064). The “limma” package of R software was used to screen out miRNAs with a significant difference. Weighted gene co-expression network analysis (WGCNA) was used to identify miRNAs associated with stroke. Cytoscape software was used to analyze and visualize the weighting network. Peripheral blood of stroke patients was collected and verified by reverse transcription-polymerase chain reaction (RT-PCR). Finally, the “pROC” package of R software was used to evaluate the value of the hub miRNAs for stroke prediction. Results: A total of 641 differentially expressed miRNAs were selected by analyzing the peripheral blood miRNA microarray data set of stroke patients. WGCNA identified miRNAs related to stroke and further analyzed them to screen out 4 pivotal genes (miR-1910-5p, miR-636, miR-7108-3p and miR-887-3p) with diagnostic value for stroke. RT-PCR confirmed that the expression of miR-1910-5p, miR-636, miR-708-3p and miR-887-3p was decreased in the peripheral blood of stroke patients. The AUC of miR-1910-5p, miR-636, miR-7108-3p and miR-887-3p in predicting stroke were 0.962, 0.970, 0.962 and 0.973, respectively. The AUC of junction miRNAs combined to predict stroke was 0.987. Conclusion: Abnormal expression of miRNAs in peripheral blood of stroke patients has diagnostic value, which provides clues for exploring the pathogenesis, diagnosis and treatment strategies of stroke.
Keywords：
stroke; microRNA; weighted gene co-expression network analysis; biomarker