Serum levels of microRNAs can specifically predict liver injury of chronic hepatitis B.
OBJECTIVE
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 correlation 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 determine the specificity and sensitivity of each individual miRNA in distinguishing patients with CHB from Ctrls.


RESULTS
miRNA profile analysis showed that 34 miRNAs were differentially expressed between CHB and Ctrl subjects, in which 12 were up-regulated and 22 down-regulated in CHB 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 < 1.00 × 10(-6)) in CHB 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 CHB (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 CHB, 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 CHB, NASH and Ctrl subjects.


CONCLUSIONS
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 potential biomarkers for liver injury caused by CHB and NASH.
Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Hui
H
Zhang
Qing-Ya
QY
Li
Zhi-Zhong
ZZ
Guo
Yan
Y
Guan
Jia
J
Du
Yi-Yu
YY
Lu
Yi-Yang
YY
Hu
Ping
P
Liu
Shuang
S
Huang
Shi-Bing
SB
Su
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D005234:Fatty Liver / Q000097:blood; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000150:complications*; D006801:Humans; D007249:Inflammation; D008099:Liver / Q000293:injuries / Q000821:virology*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012372:ROC Curve; D012680:Sensitivity and Specificity
D015415:Biomarkers; D035683:MicroRNAs