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    外周血白细胞ANAPC1表达水平与冠心病的相关性及其诊断价值

    Correlation between ANAPC1 expression level in peripheral blood leukocytes and coronary heart disease and its diagnostic value

      摘要
    • 摘要: 目的：探讨外周血白细胞（PBLs）细胞周期末期促复合体亚基1（ANAPC1）表达与冠心病（CHD）的相关性及其诊断价值。方法：从GEO数据库检索基因表达数据集和单细胞RNA测序数据集观察ANAPC1在CHD患者PBLs和其他细胞中的表达情况。通过实时荧光定量PCR（RT-qPCR）法检测和比较70例CHD患者与对照人群ANAPC1的表达水平。用受试者工作特征（ROC）曲线和总ROC（SROC）曲线评价ANAPC1对CHD的诊断价值。使用CDB数据库查找ANAPC1的潜在上游转录因子，ANAPC1差异共表达基因通过基因本体论（GO）、疾病本体论（DO）和京都基因和基因组百科全书（KEGG）进行富集分析。结果：GEO数据库分析显示，ANAPC1在CHD患者PBLs中的表达水平降低（总SMD=-0.74，95%CI：-1.36～-0.13），SROC曲线下面积为0.76，灵敏度为0.73，特异度为0.67。临床标本RT-qPCR显示，ANAPC1在CHD患者PBLs中的表达水平降低，ROC曲线下面积为0.71，灵敏度为0.80，特异度为0.61。GEO数据库查找单细胞RNA测序相关数据集发现，ANAPC1在不同时期、不同细胞中的表达量均无明显差异。上游潜在转录因子预测显示，ETS1（SMD=-0.53，95%CI：-0.99～-0.06）、GATA3（SMD=-0.46，95%CI：-0.87～-0.06）可能正向调控ANAPC1的表达，IRAK1（SMD=0.42，95%CI：0.07～0.77）、ERF（SMD=0.27，95%CI：-0.03～0.51）可能负向调控ANAPC1的表达。DO富集分析提示，ANAPC1差异负相关共表达基因与动脉粥样硬化及动脉粥样硬化性心脏病等疾病相关。结论：ANAPC1在CHD患者PBLs中的表达下调与CHD发生、发展呈正相关关系，且对CHD具有一定的诊断价值。

       

      Abstract: Objective: To investigate the correlation between anaphase-promoting complex subunit 1(ANAPC1)in peripheral blood leukocytes (PBLs) and coronary heart disease (CHD) and its diagnostic value.Methods: Gene expression datasets and single-cell RNA sequencing datasets were retrieved from the Gene Expression Omnibus (GEO) database to assess the expression of ANAPC1 in PBLs and other cells of CHD patients.Real-time fluorescence quantitative PCR(RT-qPCR)was used to detect and compare the expression level of ANAPC1 in 70 CHD patients and control samples.Receiver operating characteristic (ROC) curve and summary ROC (SROC)curve were used to evaluate the diagnostic value of ANAPC1 in CHD.The CDB database was used to search for potential upstream transcription factors of ANAPC1.ANAPC1 differentially co-expressed genes were subjected to enrichment analysis using gene ontology (GO), disease ontology (DO), and the Kyoto Encyclopedia of Genes and Genomes(KEGG).Results: GEO database analysis showed that the expression level of ANAPC1 in PBLs in CHD patients was decreased (total SMD=-0.74, 95% CI:-1.36 to-0.13), the area under SROC curve was 0.76, the sensitivity was 0.73, and the specificity was 0.67.RT-qPCR of clinical samples showed that the expression level of ANAPC1 in PBLs of CHD patients was decreased, the area under ROC curve was 0.71, the sensitivity was 0.80, and the specificity was 0.61.A search for datasets related to single-cell RNA sequencing in the GEO database revealed that the expression levels of ANAPC1 in different cells at different periods were not significantly different.The prediction of upstream potential transcription factors showed that the expression of ANAPC1 was positively regulated by ETS1 (SMD=-0.53, 95% CI:-0.99 to-0.06) and GATA3 (SMD=-0.46, 95% CI:-0.87 to-0.06)and negatively regulated by IRAK1(SMD=0.42, 95%CI:0.07 to 0.77)and ERF(SMD=0.27, 95%CI:0.03 to 0.51).DO enrichment analysis suggested that ANAPC1 differentially negatively co-expressed genes were associated with diseases such as atherosclerosis and atherosclerotic heart disease.Conclusion: The downregulation of ANAPC1 expression in PBLs in CHD patients is positively correlated with the occurrence and development of CHD, and has certain diagnostic value for CHD.

       

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