Serum MicroRNAs as Biomarkers in Hepatitis C: Preliminary Evidence of a MicroRNA Panel for the Diagnosis of Hepatocellular Carcinoma
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...
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doaj-a84dd82db9de4e738fee3544d8d30e5f2020-11-25T01:59:03ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-02-0120486410.3390/ijms20040864ijms20040864Serum MicroRNAs as Biomarkers in Hepatitis C: Preliminary Evidence of a MicroRNA Panel for the Diagnosis of Hepatocellular CarcinomaAnna Weis0Louise Marquart1Diego A. Calvopina2Berit Genz3Grant A. Ramm4Richard Skoien5Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, QLD 4006, AustraliaQIMR Berghofer Statistics Unit, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, QLD 4006, AustraliaHepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, QLD 4006, AustraliaHepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, QLD 4006, AustraliaHepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, QLD 4006, AustraliaHepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, QLD 4006, AustraliaEarly 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; <i>n</i> = 20); cirrhosis (<i>n</i> = 20); and cirrhosis with HCC (<i>n</i> = 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%; <i>p</i> < 0.001). When combined with FIB-4 or APRI, performance was improved with AUC = 0.89 (<i>p</i> < 0.001) and 0.87 (<i>p</i> < 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%; <i>p</i> < 0.001), outperforming AFP (AUC = 0.64, <i>p</i> = 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.https://www.mdpi.com/1422-0067/20/4/864serum miRNAhepatocellular carcinomacirrhosisnon-invasive biomarkerhepatitis C |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna Weis Louise Marquart Diego A. Calvopina Berit Genz Grant A. Ramm Richard Skoien |
spellingShingle |
Anna Weis Louise Marquart Diego A. Calvopina Berit Genz Grant A. Ramm Richard Skoien Serum MicroRNAs as Biomarkers in Hepatitis C: Preliminary Evidence of a MicroRNA Panel for the Diagnosis of Hepatocellular Carcinoma International Journal of Molecular Sciences serum miRNA hepatocellular carcinoma cirrhosis non-invasive biomarker hepatitis C |
author_facet |
Anna Weis Louise Marquart Diego A. Calvopina Berit Genz Grant A. Ramm Richard Skoien |
author_sort |
Anna Weis |
title |
Serum MicroRNAs as Biomarkers in Hepatitis C: Preliminary Evidence of a MicroRNA Panel for the Diagnosis of Hepatocellular Carcinoma |
title_short |
Serum MicroRNAs as Biomarkers in Hepatitis C: Preliminary Evidence of a MicroRNA Panel for the Diagnosis of Hepatocellular Carcinoma |
title_full |
Serum MicroRNAs as Biomarkers in Hepatitis C: Preliminary Evidence of a MicroRNA Panel for the Diagnosis of Hepatocellular Carcinoma |
title_fullStr |
Serum MicroRNAs as Biomarkers in Hepatitis C: Preliminary Evidence of a MicroRNA Panel for the Diagnosis of Hepatocellular Carcinoma |
title_full_unstemmed |
Serum MicroRNAs as Biomarkers in Hepatitis C: Preliminary Evidence of a MicroRNA Panel for the Diagnosis of Hepatocellular Carcinoma |
title_sort |
serum micrornas as biomarkers in hepatitis c: preliminary evidence of a microrna panel for the diagnosis of hepatocellular carcinoma |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-02-01 |
description |
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; <i>n</i> = 20); cirrhosis (<i>n</i> = 20); and cirrhosis with HCC (<i>n</i> = 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%; <i>p</i> < 0.001). When combined with FIB-4 or APRI, performance was improved with AUC = 0.89 (<i>p</i> < 0.001) and 0.87 (<i>p</i> < 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%; <i>p</i> < 0.001), outperforming AFP (AUC = 0.64, <i>p</i> = 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. |
topic |
serum miRNA hepatocellular carcinoma cirrhosis non-invasive biomarker hepatitis C |
url |
https://www.mdpi.com/1422-0067/20/4/864 |
work_keys_str_mv |
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