Altered gene expression in T-cell receptor signalling in peripheral blood leucocytes in acute coronary syndrome predicts secondary coronary events.
Altered gene expression in T-cell receptor signalling in peripheral blood leucocytes in acute coronary syndrome predicts secondary coronary events.
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DOI：
10.1136/openhrt-2016-000400
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发表时间：
2016
期刊：
影响因子：
2.7
通讯作者：
Takamura M
中科院分区：
文献类型：
--
作者：
Takashima S;Usui S;Kurokawa K;Kitano T;Kato T;Murai H;Furusho H;Oda H;Maruyama M;Nagata Y;Usuda K;Kubota K;Takeshita Y;Sakai Y;Honda M;Kaneko S;Takamura M
需要对急性冠脉综合征（ACS）患者外周血白细胞（PBL）基因表达进行全面的分析，以作为一种预测指标。我们探讨了ACS患者外周血淋巴细胞基因表达的特异性，以进行长期危险分层。30例ACS患者接受直接经皮冠状动脉介入治疗（PCI）和15名年龄匹配的成年人参加了医疗检查，从三个中心入组。收集外周血样品以提取RNA用于微阵列分析。在5年随访期间，该队列中36%的患者发生了预期的靶病变血运重建（TLR）和原发病变PCI的非致死性冠状动脉事件（NFE）。类别比较分析（p<0.005）表明，从7785个预筛选基因中提取83个基因（41个上调基因和42个下调基因），以根据NFE的发生对患者进行分类。基于基因本体论的通路分析显示，NFE与ACS中T细胞受体信号通路的基因表达改变相关。单变量t检验显示，已知调节炎症的死亡相关蛋白激酶1（DAPK 1）的表达水平是事件组中最显著的负调节基因（0.61倍，p<0.0005）。根据基线特征或临床生物标志物调整的Kaplan-Meier曲线分析和多变量分析表明，PBL中较低的DAPK 1表达是NFE的独立风险因素（HR：8.73; CI 1.05至72.8，p=0.045）。ACS患者外周血淋巴细胞中T细胞受体信号传导基因表达的改变可能是继发性冠状动脉事件的一个预测因子。UMIN 000001932;结果。
Comprehensive profiling of gene expression in peripheral blood leucocytes (PBLs) in patients with acute coronary syndrome (ACS) as a prognosticator is needed. We explored the specific profile of gene expression in PBLs in ACS for long-term risk stratification. 30 patients with ACS who underwent primary percutaneous coronary intervention (PCI) and 15 age-matched adults who participated in medical check-ups were enrolled from three centres. Peripheral blood samples were collected to extract RNA for microarray analyses. During the 5-year follow-up, 36% of this cohort developed the expected non-fatal coronary events (NFEs) of target lesion revascularisation (TLR) and PCI for a de novo lesion. Class comparison analysis (p<0.005) demonstrated that 83 genes among 7785 prefiltered genes (41 upregulated vs 42 downregulated genes) were extracted to classify the patients according to the occurrence of NFE. Pathway analysis based on gene ontology revealed that the NFEs were associated with altered gene expression regarding the T-cell receptor signalling pathway in ACS. Univariate t test showed that the expression level of death-associated protein kinase1 (DAPK1), known to regulate inflammation, was the most significantly negatively regulated gene in the event group (0.61-fold, p<0.0005). Kaplan-Meier curve analysis and multivariate analysis adjusted for baseline characteristics or clinical biomarkers demonstrated that lower DAPK1 expression in PBL emerged as an independent risk factor for the NFEs (HR: 8.73; CI 1.05 to 72.8, p=0.045). Altered gene expression in T-cell receptor signalling in PBL in ACS could be a prognosticator for secondary coronary events. UMIN000001932; Results.