Circulating microRNAs as a Fingerprint for Liver Cirrhosis
Circulating microRNAs as a Fingerprint for Liver Cirrhosis
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循环 microRNA 作为肝硬化的指纹
DOI：
10.1371/journal.pone.0066577
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发表时间：
2013-06-21
期刊：
影响因子：
3.7
通讯作者：
Shen, Xi-Zhong
中科院分区：
文献类型：
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作者：
Chen, Yan-Jie;Zhu, Ji-Min;Shen, Xi-Zhong
背景 对肝硬化进行灵敏和特异的检测是对疾病活动进行最佳个体化管理的迫切需要。大量研究已确定循环 miRNA 可作为包括慢性肝病在内的多种疾病的生物标志物。在这项研究中，我们研究了血浆 miRNA 特征，将其作为无症状肝硬化的潜在诊断生物标志物。方法 首先在 80 个血浆样本中进行全基因组 miRNA 微阵列分析。选择六种候选 miRNA，然后通过 qPCR 在 CHB 相关肝硬化和对照中进行训练。分类器 miR-106b 和 miR-181b 最终在两个独立队列中得到验证，其中分别包括 CHB 相关的无症状肝硬化和对照，以及非 CHB 相关的肝硬化和对照作为验证集。结果 2 个 miRNA（miR-106b 和 miR-181b）的谱被确定为肝硬化生物标志物，无论病因如何。由这两个 miRNA 构建的分类器为肝硬化提供了很高的诊断准确性（训练集中 CHB 相关肝硬化 AUC = 0.882，一个验证集中 CHB 相关无症状肝硬化为 0.774，另一验证集中非 CHB 相关肝硬化为 0.915）。结论 miR-106b和miR-181b联合检测对肝硬化患者尤其是早期肝硬化患者的诊断具有重要的临床价值。
Background Sensitive and specific detection of liver cirrhosis is an urgent need for optimal individualized management of disease activity. Substantial studies have identified circulation miRNAs as biomarkers for diverse diseases including chronic liver diseases. In this study, we investigated the plasma miRNA signature to serve as a potential diagnostic biomarker for silent liver cirrhosis. Methods A genome-wide miRNA microarray was first performed in 80 plasma specimens. Six candidate miRNAs were selected and then trained in CHB-related cirrhosis and controls by qPCR. A classifier, miR-106b and miR-181b, was validated finally in two independent cohorts including CHB-related silent cirrhosis and controls, as well as non−CHB-related cirrhosis and controls as validation sets, respectively. Results A profile of 2 miRNAs (miR-106b and miR-181b) was identified as liver cirrhosis biomarkers irrespective of etiology. The classifier constructed by the two miRNAs provided a high diagnostic accuracy for cirrhosis (AUC = 0.882 for CHB-related cirrhosis in the training set, 0.774 for CHB-related silent cirrhosis in one validation set, and 0.915 for non−CHB-related cirrhosis in another validation set). Conclusion Our study demonstrated that the combined detection of miR-106b and miR-181b has a considerable clinical value to diagnose patients with liver cirrhosis, especially those at early stage.