Abstract

BackgroundLong non-coding RNAs (lncRNAs) have been applied as biomarkers in many diseases. However, scarce biomarkers are available in single lncRNA differential expression associated with different clinical stages of liver cirrhosis (LC). The aim of the study is to identify some lncRNAs that can serve as non-invasive sensitive biomarkers for early diagnosis and grade of LC.MethodsBlood lncRNA expression was evaluated in three independent cohorts with 305 participants including healthy controls, hepatitis B virus (HBV) carriers, and patients with chronic hepatitis B (CHB) or LC. First, candidate lncRNAs were screened by CapitalBiotech microarray to diagnose cirrhosis. Quantitative reverse-transcriptase polymerase chain reaction was then used to investigate the expression of selected lncRNAs in the whole group of cirrhosis and different Child–Pugh classes. Ultimately, the diagnostic accuracy of the promising biomarker was examined and validated via Mann–Whitney test and receiver-operating characteristics analysis.ResultsLnc-TCL6 was identified as a sensitive biomarker for early diagnosis of LC (Child–Pugh A) compared with healthy controls (area under the ROC curve [AUC] = 0.636), HBV carriers (AUC = 0.671), and CHB patients (AUC = 0.672). Furthermore, lnc-TCL6 showed a favourable capacity in discriminating among different Child–Pugh classes (AUC: 0.711–0.837). Compared with healthy controls, HBV carriers, and CHB patients, the expression of lnc-TCL6 was obviously up-regulated in Child–Pugh A patients and, conversely, significantly down-regulated in Child–Pugh C patients.ConclusionsLnc-TCL6 is a novel potential biomarker for early diagnosis of LC and is a possible predictor of disease progression.

Highlights

  • Advanced liver cirrhosis (LC) is currently a common cause of death [1]

  • Discovery phase: microarray profiling of Long non-coding RNAs (lncRNAs) associated with hepatitis B virus (HBV)-related LC

  • According to the analysis of the microarray and data summarization, ENST00000602692.1, ENST00000589723.1, lnc-CTA-250D10.23, ENST00000527317.2, TCONS_00023502, and lnc-TCL6 were identified as candidate biomarkers with significantly higher expression levels in the LC group than in the healthy group

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Summary

Introduction

Advanced liver cirrhosis (LC) is currently a common cause of death [1]. LC is one of the top 20 causes of disability and loss of life, accounting for 1.6% of the worldwide burden [2]. Far, these studies have lacked accurate expression of lncRNA in LC tissues or peripheral blood To fill this gap, our study aims to verify a potential lncRNA biomarker for early onset and predict the progress of hepatitis B virus (HBV)-related LC. Methods: Blood lncRNA expression was evaluated in three independent cohorts with 305 participants including healthy controls, hepatitis B virus (HBV) carriers, and patients with chronic hepatitis B (CHB) or LC. Results: Lnc-TCL6 was identified as a sensitive biomarker for early diagnosis of LC (Child–Pugh A) compared with healthy controls (area under the ROC curve [AUC] 1⁄4 0.636), HBV carriers (AUC 1⁄4 0.671), and CHB patients (AUC 1⁄4 0.672). Conclusions: Lnc-TCL6 is a novel potential biomarker for early diagnosis of LC and is a possible predictor of disease progression

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