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Serum lincRNA‐p21 as a potential biomarker of liver fibrosis in chronic hepatitis B patients
Authors:XuFei Fan  Guojun Li  Bicheng Chen  Peihong Dong  Jianjian Zheng
Affiliation:1. Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China;2. Department of Hepatology, Ningbo Yinzhou Second Hospital, Ningbo, Zhejiang, China;3. Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China;4. Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Abstract: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.
Keywords:chronic hepatitis B  hepatic stellate cells  lincRNA‐p21  liver fibrosis  promoter methylation
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