Yu Fujun, Zhou Guangyao, Huang Kate, Fan XuFei, Li Guojun, Chen Bicheng, Dong Peihong, Zheng Jianjian
Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Infectious Diseases, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
J Viral Hepat. 2017 Jul;24(7):580-588. doi: 10.1111/jvh.12680. Epub 2017 Feb 9.
Serum long non-coding RNAs (lncRNAs) are emerging as promising biomarkers for various human diseases. The aim of this study was to investigate the feasibility of using serum long intergenic non-coding RNA-p21 (lincRNA-p21) as a biomarker for chronic hepatitis B patients. Serum lincRNA-p21 levels were quantified using real-time PCR in 417 CHB patients and 363 healthy controls. The promoter methylation level of lincRNA-p21 was detected using bisulphite-sequencing analysis in primary hepatic stellate cells (HSCs). Sera from hepatitis B-infected patients contained lower levels of lincRNA-p21 than sera from healthy controls. Serum lincRNA-p21 levels negatively correlated with stages of liver fibrosis in infected patients. Receiver operating characteristic (ROC) curve analyses suggested that serum lincRNA-p21 had a significant diagnostic value for liver fibrosis in these patients. It yielded an area under the curve of ROC of 0.854 with 100% sensitivity and 70% specificity in discriminating liver fibrosis from healthy controls. There was additionally a negative correlation between serum lincRNA-p21 level and the markers of liver fibrosis including α-SMA and Col1A1. However, there was no correlation of serum lincRNA-p21 level with the markers of viral replication, liver inflammatory activity, and liver function. Notably, during primary HSCs culture, loss of lincRNA-p21 expression was associated with promoter methylation. Serum lincRNA-p21 could serve as a potential biomarker of liver fibrosis in CHB patients. Down-regulation of lincRNA-p21 in liver fibrosis may be associated with promoter methylation.
血清长链非编码RNA（lncRNAs）正逐渐成为各种人类疾病有前景的生物标志物。本研究的目的是探讨使用血清长链基因间非编码RNA-p21（lincRNA-p21）作为慢性乙型肝炎患者生物标志物的可行性。采用实时定量PCR对417例慢性乙型肝炎患者和363例健康对照者的血清lincRNA-p21水平进行定量。采用亚硫酸氢盐测序分析法检测原代肝星状细胞（HSCs）中lincRNA-p21的启动子甲基化水平。乙型肝炎感染患者的血清中lincRNA-p21水平低于健康对照者的血清。感染患者血清lincRNA-p21水平与肝纤维化分期呈负相关。受试者工作特征（ROC）曲线分析表明，血清lincRNA-p21对这些患者的肝纤维化具有显著的诊断价值。在区分肝纤维化与健康对照时，其ROC曲线下面积为0.854，敏感性为100%，特异性为70%。此外，血清lincRNA-p21水平与肝纤维化标志物α-SMA和Col1A1之间也呈负相关。然而，血清lincRNA-p21水平与病毒复制标志物、肝脏炎症活动和肝功能之间无相关性。值得注意的是，在原代肝星状细胞培养过程中，lincRNA-p21表达的缺失与启动子甲基化有关。血清lincRNA-p21可作为慢性乙型肝炎患者肝纤维化的潜在生物标志物。肝纤维化中lincRNA-p21的下调可能与启动子甲基化有关。
