Serum levels of microRNAs can specifically predict liver injury of chronic hepatitis B

• Published in: World journal of gastroenterology : WJG Vol. 18; no. 37; pp. 5188 - 5196
• Main Authors: Zhang, Hui, Li, Qing-Ya, Guo, Zhi-Zhong, Guan, Yan, Du, Jia, Lu, Yi-Yu, Hu, Yi-Yang, Liu, Ping, Huang, Shuang, Su, Shi-Bing
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Co., Limited 07.10.2012
• Subjects: Adult; Biomarkers - metabolism; Case-Control Studies; Fatty Liver - blood; Female; Gene Expression Profiling - methods; Hepatitis B, Chronic - blood; Hepatitis B, Chronic - complications; Humans; Inflammation; Liver - injuries; Liver - virology; Male; microRNA; MicroRNAs - metabolism; Middle Aged; miRNA; Oligonucleotide Array Sequence Analysis; Original; ROC Curve; Sensitivity and Specificity; 典型相关分析; 慢性乙型肝炎; 肝损伤; 血清样品; 逆转录聚合酶链反应; 预测; Chronic hepatitis B; Nonalcohlic steatohepatitis; Serum microRNAs; Liver injury
• ISSN: 1007-9327; 2219-2840; 2219-2840
• DOI: 10.3748/wjg.v18.i37.5188

AIM： To investigate whether circulating microRNAs （miRNAs） can serve as molecular markers to predict liver injury resulted from chronic hepatitis B （CHB）. METHODS： The profiles of serum miRNA expression were first generated with serum samples collected from 10 patients with CHB and 10 healthy donors （Ctrls） by microarray analysis. The levels of several miRNAs were further quantitated by real-time reverse transcription polymerase chain reaction with serum samples from another 24 CHB patients and 24 Ctrls. Serum samples of 20 patients with nonalcohlic steatohepatitis （NASH） were also included for comparison. The comparison in the levels of miRNAs between groups （CHB, NASH and Ctrl） was analyzed with Mann-Whitney U-test. The cor- relation between miRNAs and clinical pathoparameters was analyzed using Spearman correlation analysis or canonical correlation analysis. The receiver-operator characteristic （ROC） curves were also generated to de- termine the specificity and sensitivity of each individual miRNA in distinguishing patients with CriB from Ctrls. RESULTS： miRNA profile analysis showed that 34 miR- NAs were differentially expressed between CriB and Ctrl subjects, in which 12 were up-regulated and 22 down-regulated in CriB subject （fold change 〉 2.0 and P 〈 0.01）. The median levels of miR-122, -572, -575 and -638 were significantly higher （P 〈 1.00 × 10-5） while miR-744 significantly lower （P 〈 1.0× 10-6） in Crib compared with the Ctrl. The levels of miR-122, -572 and -638 were also higher （P 〈 1.00×10-3） while the level of miR-744 lower in CriB （P 〈 0.05） than in NASH, although the difference between them was not as significant as that between CHB and Ctrl. ROC curve analysis revealed that the levels of miR-122, -572, -575, -638 and -744 in serum were sensitive and specific enough to distinguish CriB, NASH and Ctrl. Multivariate analysis further showed that the levels of these miRNAs were correlated with the liver function parameters. Most significantly, it was the scatter plot of principal component with the levels of these miRNAs, but not the parameters of liver function, which clearly distinguished CriB, NASH and Ctrl subjects. CONCLUSION： Serum levels of miR-122, -572, -575, -638 and -744 are deregulated in patients with CHB or NASH. The levels of these miRNAs may serve as po- tential biomarkers for liver injury caused by CHB and NASH.