SERUM miRNA AS A USEFUL BIOMARKER FOR DIAGNOSIS OF NASH

초록

Background: Non-alcoholic steatohepatitis(NASH), as subtype of non-alcoholic fatty liver disease(NAFLD), is progressive disease that can result in advanced fibrosis and cirrhosis. The aim of this study was to evaluate diagnostic value using serum miRNA to distinguish NASH from non-alcoholic fatty liver(NAFL). Methods: RNA extraction and small RNA sequencing were done using sera from 24 patients who were diagnosed with NAFLD by biopsy. miRNA expression levels were compared between 12 NAFL patients and 12 NASH patients. After selecting miRNAs showing significantly increased expression in NASH group comparing to NAFL group, diagnostic accuracies of each miRNA and a combination of miRNAs were analysed. For functional relationship between specific signalling pathway and miRNAs that were significantly elevated in sera of NASH patients compared to those in sera of NAFL patients, miEAA database was used. Results: A total of 2,588 mature miRNA reads were obtained from miRDeep2 Quantifier module. Expression levels of 26 miRNAs were significantly increased in NASH group than in NAFL group, whereas those of 12 miRNAs were significantly decreased in NASH group than in NAFL group. Among 38 significant miRNAs, eight miRNAs that showed high expression within the top 25% of all miRNAs were selected and compared. Only four miRNAs showed meaningful area under receiver operating characteristic(AUROC) values for NASH diagnosis (P < 0.05). When AUROC values for diagnosis of NASH were compared between a combination of 8 miRNAs (miR-15-3p, miR-21-5p, miR-29b-3p, miR-126-5p, miR151a-3p, miR-183-5p, miR-192-5p, and miR-4449) (AUROC: 0.924; 95% CI: 0.739-0.992) and a combination of 4 miRNAs (miR-21-5p, miR151a-3p, miR-192-5p, and miR-4449) (AUROC: 0.875; 95% CI: 0.676-0.973), there was no significant difference (P = 0.26). Among 26 miRNAs that showed significantly increased expression in NASH group, 10 miRNAs were included in 17 miRNA group, such as adipocytokine signalling pathway and thyroid hormone signalling pathway. Conclusion: Combination of serum circulating miRNAs could be used as novel biomarker for diagnosis of NASH. The expression of circulating miRNAs is correlated with specific signalling pathway.