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Int J Mol Sci. 2019 Feb 17;20(4). pii: E864. doi: 10.3390/ijms20040864.

Serum MicroRNAs as Biomarkers in Hepatitis C: Preliminary Evidence of a MicroRNA Panel for the Diagnosis of Hepatocellular Carcinoma.

Author information

1
Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, QLD 4006, Australia. anna.weis1@uqconnect.edu.au.
2
Faculty of Medicine, University of Queensland, Herston Road, Herston, QLD 4006, Australia. anna.weis1@uqconnect.edu.au.
3
QIMR Berghofer Statistics Unit, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, QLD 4006, Australia. Louise.Marquart@qimrberghofer.edu.au.
4
Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, QLD 4006, Australia. Diego.Calvopina@qimrberghofer.edu.au.
5
Faculty of Medicine, University of Queensland, Herston Road, Herston, QLD 4006, Australia. Diego.Calvopina@qimrberghofer.edu.au.
6
Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, QLD 4006, Australia. Berit.Genz@qimrberghofer.edu.au.
7
Faculty of Medicine, University of Queensland, Herston Road, Herston, QLD 4006, Australia. Berit.Genz@qimrberghofer.edu.au.
8
Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, QLD 4006, Australia. Grant.Ramm@qimrberghofer.edu.au.
9
Faculty of Medicine, University of Queensland, Herston Road, Herston, QLD 4006, Australia. Grant.Ramm@qimrberghofer.edu.au.
10
Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, QLD 4006, Australia. Richard.Skoien@health.qld.gov.au.
11
Faculty of Medicine, University of Queensland, Herston Road, Herston, QLD 4006, Australia. Richard.Skoien@health.qld.gov.au.
12
Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Bowen Bridge Rd & Butterfield St, Herston, QLD 4029, Australia. Richard.Skoien@health.qld.gov.au.

Abstract

Early diagnosis of cirrhosis and hepatocellular carcinoma (HCC) due to chronic Hepatitis C (CHC) remain clinical priorities. In this pilot study, we assessed serum microRNA (miRNA) expression to distinguish cirrhosis and HCC, alone and in combination with the aminotransferase-to-platelet ratio (APRI), Fibrosis 4 (FIB-4), and alpha-fetoprotein (AFP). Sixty CHC patients were subdivided into 3 cohorts: Mild disease (fibrosis stage F0-2; n = 20); cirrhosis (n = 20); and cirrhosis with HCC (n = 20). Circulating miRNA signatures were determined using a liver-specific real-time quantitative reverse transcription PCR (qRT-PCR) microarray assessing 372 miRNAs simultaneously. Differentially-expressed miRNA candidates were independently validated using qRT-PCR. Serum miRNA-409-3p was increased in cirrhosis versus mild disease. In HCC versus cirrhosis, miRNA-486-5p was increased, whereas miRNA-122-5p and miRNA-151a-5p were decreased. A logistic regression model-generated panel, consisting of miRNA-122-5p + miRNA-409-3p, distinguished cirrhosis from mild disease (area under the curve, AUC = 0.80; sensitivity = 85%, specificity = 70%; p < 0.001). When combined with FIB-4 or APRI, performance was improved with AUC = 0.89 (p < 0.001) and 0.87 (p < 0.001), respectively. A panel consisting of miRNA-122-5p + miRNA-486-5p + miRNA-142-3p distinguished HCC from cirrhosis (AUC = 0.94; sensitivity = 80%, specificity = 95%; p < 0.001), outperforming AFP (AUC = 0.64, p = 0.065). Serum miRNAs are differentially expressed across the spectrum of disease severity in CHC. MicroRNAs have great potential as diagnostic biomarkers in CHC, particularly in HCC where they outperform the only currently-used biomarker, AFP.

KEYWORDS:

cirrhosis; hepatitis C; hepatocellular carcinoma; non-invasive biomarker; serum miRNA

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