目的:探讨精氨酸酶1 (arginase 1, ARG1)在冠状动脉性心脏病(coronary heart disease, CHD)中的转录表达水平及潜在致病机理。方法:整合CHD相关多中心高通量数据,计算ARG1 mRNA表达水平标准化平均差(standardized mean difference, SMD)...目的:探讨精氨酸酶1 (arginase 1, ARG1)在冠状动脉性心脏病(coronary heart disease, CHD)中的转录表达水平及潜在致病机理。方法:整合CHD相关多中心高通量数据,计算ARG1 mRNA表达水平标准化平均差(standardized mean difference, SMD),通过汇总受试者工作特征曲线,灵敏度,特异度,似然比等指标来评价ARG1在CHD中的临床病理意义。利用孟德尔随机化法确定ARG1和CHD之间的因果联系,最后通过京都基因与基因组百科全书以及蛋白质–蛋白质相互作用分析明确ARG1在CHD中的潜在调控机制。结果:本研究共纳入6个平台14个CHD数据集,含427例CHD样本,296例正常对照样本。ARG1表达在CHD中显著上调,其标准化平均差为0.44 (95% CI: 0.06~0.83),汇总受试者工作特征曲线下面积为0.72 (95% CI: 0.68~0.76),灵敏度为0.55 (95% CI: 0.36~0.73),特异度为0.79 (95% CI: 0.55~0.92),阳性似然比为2.61 (95% CI: 1.16~5.86)、阴性似然比为0.57 (95% CI: 0.38~0.85);孟德尔随机化法未见ARG1与CHD之间的显著关联(OR = 0.9833, 95% CI = 0.9408~1.0278, p = 0.4563);ARG1可通过部分信号通路影响CHD的进展,如利什曼病、中性粒细胞胞外陷阱的形成、癌症中PD-L1表达和PD-1检查点等通路。结论:ARG1可能作为促进CHD发生的关键基因参与疾病的发生发展。Objective: To investigate the transcriptional expression levels of arginase 1 (ARG1) in coronary heart disease (CHD) and its potential pathogenic mechanisms. Methods: Integrating multi-center high-throughput data related to CHD, we computed the standardized mean difference (SMD) of ARG1 mRNA expression levels. The clinical pathological significance of ARG1 in CHD was evaluated through aggregated receiver operating characteristic curves, sensitivity, specificity, and likelihood ratios. Mendelian randomization was employed to determine the causal relationship between ARG1 and CHD. The potential regulatory mechanisms of ARG1 in CHD were clarified through the Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction analyses. Results: This study included 14 CHD datasets from 6 platforms, comprising 427 CHD samples and 296 normal control samples. ARG1 expression was significantly upregulated in CHD, with a standardized mean difference of 0.44 (95% CI: 0.06 to 0.83). The area under the summary receiver operating characteristic curve was 0.72 (95% CI: 0.68 to 0.76), sensitivity was 0.55 (95% CI: 0.36 to 0.73), specificity was 0.79 (95% CI: 0.55 to 0.92), the positive likelihood ratio was 2.61 (95% CI: 1.16 to 5.86), and the negative likelihood ratio was 0.57 (95% CI: 0.38 to 0.85). Mendelian randomization did not show a significant association between ARG1 and CHD (OR = 0.9833, 95% CI = 0.9408 to 1.0278, p = 0.4563). ARG1 could influence the progression of CHD through several signaling pathways, including those involved in leishmaniasis, neutrophil extracellular traps formation, and PD-L1 expression in cancer and PD-1 checkpoint pathways. Conclusion: ARG1 may act as a key gene promoting the onset and progression of CHD.展开更多
文摘目的:探讨精氨酸酶1 (arginase 1, ARG1)在冠状动脉性心脏病(coronary heart disease, CHD)中的转录表达水平及潜在致病机理。方法:整合CHD相关多中心高通量数据,计算ARG1 mRNA表达水平标准化平均差(standardized mean difference, SMD),通过汇总受试者工作特征曲线,灵敏度,特异度,似然比等指标来评价ARG1在CHD中的临床病理意义。利用孟德尔随机化法确定ARG1和CHD之间的因果联系,最后通过京都基因与基因组百科全书以及蛋白质–蛋白质相互作用分析明确ARG1在CHD中的潜在调控机制。结果:本研究共纳入6个平台14个CHD数据集,含427例CHD样本,296例正常对照样本。ARG1表达在CHD中显著上调,其标准化平均差为0.44 (95% CI: 0.06~0.83),汇总受试者工作特征曲线下面积为0.72 (95% CI: 0.68~0.76),灵敏度为0.55 (95% CI: 0.36~0.73),特异度为0.79 (95% CI: 0.55~0.92),阳性似然比为2.61 (95% CI: 1.16~5.86)、阴性似然比为0.57 (95% CI: 0.38~0.85);孟德尔随机化法未见ARG1与CHD之间的显著关联(OR = 0.9833, 95% CI = 0.9408~1.0278, p = 0.4563);ARG1可通过部分信号通路影响CHD的进展,如利什曼病、中性粒细胞胞外陷阱的形成、癌症中PD-L1表达和PD-1检查点等通路。结论:ARG1可能作为促进CHD发生的关键基因参与疾病的发生发展。Objective: To investigate the transcriptional expression levels of arginase 1 (ARG1) in coronary heart disease (CHD) and its potential pathogenic mechanisms. Methods: Integrating multi-center high-throughput data related to CHD, we computed the standardized mean difference (SMD) of ARG1 mRNA expression levels. The clinical pathological significance of ARG1 in CHD was evaluated through aggregated receiver operating characteristic curves, sensitivity, specificity, and likelihood ratios. Mendelian randomization was employed to determine the causal relationship between ARG1 and CHD. The potential regulatory mechanisms of ARG1 in CHD were clarified through the Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction analyses. Results: This study included 14 CHD datasets from 6 platforms, comprising 427 CHD samples and 296 normal control samples. ARG1 expression was significantly upregulated in CHD, with a standardized mean difference of 0.44 (95% CI: 0.06 to 0.83). The area under the summary receiver operating characteristic curve was 0.72 (95% CI: 0.68 to 0.76), sensitivity was 0.55 (95% CI: 0.36 to 0.73), specificity was 0.79 (95% CI: 0.55 to 0.92), the positive likelihood ratio was 2.61 (95% CI: 1.16 to 5.86), and the negative likelihood ratio was 0.57 (95% CI: 0.38 to 0.85). Mendelian randomization did not show a significant association between ARG1 and CHD (OR = 0.9833, 95% CI = 0.9408 to 1.0278, p = 0.4563). ARG1 could influence the progression of CHD through several signaling pathways, including those involved in leishmaniasis, neutrophil extracellular traps formation, and PD-L1 expression in cancer and PD-1 checkpoint pathways. Conclusion: ARG1 may act as a key gene promoting the onset and progression of CHD.
