Wang Tie-Zheng, Lin Dong-Dong, Jin Bo-Xun, Sun Xiang-Ying, Li Ning
Department of General Surgery, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.
Beijing QuantoBio Biotechnology Co. Ltd., Beijing Economic-Technological Development Area, Beijing 100176, P.R. China.
Exp Ther Med. 2019 Mar;17(3):1919-1929. doi: 10.3892/etm.2018.7117. Epub 2018 Dec 19.
The aim of the present study was to evaluate the potential use of 7 plasma miRNAs for liver fibrosis staging in patients with chronic hepatitis B virus (HBV) infection. Relative levels of miRNAs were measured using quantitative polymerase chain reaction and used to develop a diagnostic panel. A receiver operating characteristic (ROC) curve was drawn to evaluate the performance of individual miRNAs and the whole panel. It was identified that hsa-miR-122 exhibited significantly different expression levels between F4 and F3, F2, F1, and F0 fibrosis stages (P<0.05), and between F2 and F1 stages (P=0.045); hsa-miR-146a-5p, hsa-miR-29c-3p and hsa-miR-223 exhibited significantly different expression levels between F4 and F0 stages. ROC analysis revealed that hsa-miR-122-5p, hsa-miR-223 and hsa-miR-29c-3p identified patients with ≥F2 fibrosis with area under the curve (AUC) =0.745, 0.631 and 0.670, respectively. hsa-miR-122-5p identified patients with ≥F3 disease (AUC=0.783). hsa-miR-122-5p, hsa-miR-223 and hsa-miR-29c-3p identified patients with cirrhosis with AUC=0.776, 0.617 and 0.619, respectively. The miRNA panel exhibited a higher accuracy compared with individual miRNAs in discriminating between ≥F2, ≥F3 and F4 fibrosis stages with AUC=0.904, 0.889 and 0.835, respectively. hsa-miR-122-5p, hsa-miR-146a, hsa-miR-29c and hsa-miR-223 were positively correlated with fibrosis stage. hsa-miR-122-5p and hsa-miR-381-3p were negatively correlated with alanine aminotransferase, aspartate transaminase and HBV viral DNA load. These 7 miRNAs may serve as potential biomarkers of liver fibrosis in patients with HBV-associated fibrosis. The miRNA panel may serve as a novel non-invasive method for liver fibrosis staging.
本研究的目的是评估7种血浆微小RNA（miRNA）在慢性乙型肝炎病毒（HBV）感染患者肝纤维化分期中的潜在应用价值。使用定量聚合酶链反应测量miRNA的相对水平，并用于构建诊断模型。绘制受试者工作特征（ROC）曲线以评估单个miRNA和整个模型的性能。结果发现，hsa-miR-122在F4与F3、F2、F1和F0纤维化阶段之间表现出显著不同的表达水平（P<0.05），在F2与F1阶段之间也有显著差异（P=0.045）；hsa-miR-146a-5p、hsa-miR-29c-3p和hsa-miR-223在F4与F0阶段之间表现出显著不同的表达水平。ROC分析显示，hsa-miR-122-5p、hsa-miR-223和hsa-miR-29c-3p分别以曲线下面积（AUC）=0.745、0.631和0.670识别出纤维化程度≥F2的患者。hsa-miR-122-5p识别出疾病程度≥F3的患者（AUC=0.783）。hsa-miR-122-5p、hsa-miR-223和hsa-miR-29c-3p分别以AUC=0.776、0.617和0.619识别出肝硬化患者。在区分纤维化程度≥F2、≥F3和F4阶段时，miRNA模型比单个miRNA表现出更高的准确性，其AUC分别为0.904、0.889和0.835。hsa-miR-122-5p、hsa-miR-146a、hsa-miR-29c和hsa-miR-22与纤维化阶段呈正相关。hsa-miR-122-5p和hsa-miR-381-3p与丙氨酸转氨酶、天冬氨酸转氨酶和HBV病毒载量呈负相关。这7种miRNA可能作为HBV相关纤维化患者肝纤维化的潜在生物标志物。miRNA模型可能作为一种新的肝纤维化分期的非侵入性方法。
