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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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Autores principales: Weis, Anna, Marquart, Louise, Calvopina, Diego A., Genz, Berit, Ramm, Grant A., Skoien, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412219/
https://www.ncbi.nlm.nih.gov/pubmed/30781550
http://dx.doi.org/10.3390/ijms20040864
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author Weis, Anna
Marquart, Louise
Calvopina, Diego A.
Genz, Berit
Ramm, Grant A.
Skoien, Richard
author_facet Weis, Anna
Marquart, Louise
Calvopina, Diego A.
Genz, Berit
Ramm, Grant A.
Skoien, Richard
author_sort Weis, Anna
collection PubMed
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; 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.
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spelling pubmed-64122192019-04-05 Serum MicroRNAs as Biomarkers in Hepatitis C: Preliminary Evidence of a MicroRNA Panel for the Diagnosis of Hepatocellular Carcinoma Weis, Anna Marquart, Louise Calvopina, Diego A. Genz, Berit Ramm, Grant A. Skoien, Richard Int J Mol Sci Article 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. MDPI 2019-02-17 /pmc/articles/PMC6412219/ /pubmed/30781550 http://dx.doi.org/10.3390/ijms20040864 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Weis, Anna
Marquart, Louise
Calvopina, Diego A.
Genz, Berit
Ramm, Grant A.
Skoien, Richard
Serum MicroRNAs as Biomarkers in Hepatitis C: Preliminary Evidence of a MicroRNA Panel for the Diagnosis of Hepatocellular Carcinoma
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412219/
https://www.ncbi.nlm.nih.gov/pubmed/30781550
http://dx.doi.org/10.3390/ijms20040864
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