title: Serum lincRNA-p21 as a potential biomarker of liver fibrosis in chronic hepatitis B patients.
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.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Fujun
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Guangyao
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Kate
authors.initials: K
authors.lastname: Huang
authors.affiliation: Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: XuFei
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Hepatology, Ningbo Yinzhou Second Hospital, Ningbo, Zhejiang, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
authors.affiliation: Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Bicheng
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Peihong
authors.initials: P
authors.lastname: Dong
authors.affiliation: Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Jianjian
authors.identifier: 0000-0003-0563-2229
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000097:blood*; D060888:Real-Time Polymerase Chain Reaction; D044967:Serum / Q000737:chemistry*
chemical_list: D015415:Biomarkers; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D062085:RNA, Long Noncoding
keywords: chronic hepatitis B; hepatic stellate cells; lincRNA-p21; liver fibrosis; promoter methylation