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Serum miRNA Are Promising Biomarkers for the Detection of Early Hepatocellular Carcinoma after Treatment with Direct-Acting Antivirals

Direct antiviral agents (DAAs) have excellent efficacy against chronic hepatitis C virus (HCV) infection. Despite this strength, recent studies raised concerns about an unexpected hepatocellular carcinoma (HCC) occurrence rate after DAA therapy. In this exploratory case-control study, we evaluated t...

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Autores principales: Pascut, Devis, Cavalletto, Luisa, Pratama, Muhammad Yogi, Bresolin, Silvia, Trentin, Luca, Basso, Giuseppe, Bedogni, Giorgio, Tiribelli, Claudio, Chemello, Liliana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895878/
https://www.ncbi.nlm.nih.gov/pubmed/31717959
http://dx.doi.org/10.3390/cancers11111773
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author Pascut, Devis
Cavalletto, Luisa
Pratama, Muhammad Yogi
Bresolin, Silvia
Trentin, Luca
Basso, Giuseppe
Bedogni, Giorgio
Tiribelli, Claudio
Chemello, Liliana
author_facet Pascut, Devis
Cavalletto, Luisa
Pratama, Muhammad Yogi
Bresolin, Silvia
Trentin, Luca
Basso, Giuseppe
Bedogni, Giorgio
Tiribelli, Claudio
Chemello, Liliana
author_sort Pascut, Devis
collection PubMed
description Direct antiviral agents (DAAs) have excellent efficacy against chronic hepatitis C virus (HCV) infection. Despite this strength, recent studies raised concerns about an unexpected hepatocellular carcinoma (HCC) occurrence rate after DAA therapy. In this exploratory case-control study, we evaluated the potential use of miRNAs as serum biomarkers for the detection of early HCC in DAA-treated patients. In the discovery phase, the circulating miRNome was assessed in 10 matched patients with (HCC+) or without HCC (HCC−) occurrence. Microarray analysis was performed before (T0) and after one month of the DAA therapy (T1). MiRNAs discriminating HCC+ and HCC− patients were validated in 60 samples by means of RT-qPCR. We estimated the time-averaged difference of a given miRNA between HCC+ and HCC− patients using a bootstrapped random-effect generalized least square regression model (RE-GLS). At T0, miR-1207-5p, miR-1275, miR-3197, miR-4443, miR-3178, miR-483-5p, miR-4706, miR-4793-3p and miR-1246 discriminated HCC+ from HCC− patients (p < 0.05). At T1, only miR-1180-3p, miR-1228-3p, miR-4329 and miR-4484 (p < 0.05) discriminated HCC+ from HCC− patients. The subsequent validation phase identified miR-3197 as changing with both disease and time. Our results suggest that patients might be already committed to HCC occurrence before DAA therapy. MiR-3197 shows some potential for the identification of patients at risk of HCC during DAA treatments.
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spelling pubmed-68958782019-12-24 Serum miRNA Are Promising Biomarkers for the Detection of Early Hepatocellular Carcinoma after Treatment with Direct-Acting Antivirals Pascut, Devis Cavalletto, Luisa Pratama, Muhammad Yogi Bresolin, Silvia Trentin, Luca Basso, Giuseppe Bedogni, Giorgio Tiribelli, Claudio Chemello, Liliana Cancers (Basel) Article Direct antiviral agents (DAAs) have excellent efficacy against chronic hepatitis C virus (HCV) infection. Despite this strength, recent studies raised concerns about an unexpected hepatocellular carcinoma (HCC) occurrence rate after DAA therapy. In this exploratory case-control study, we evaluated the potential use of miRNAs as serum biomarkers for the detection of early HCC in DAA-treated patients. In the discovery phase, the circulating miRNome was assessed in 10 matched patients with (HCC+) or without HCC (HCC−) occurrence. Microarray analysis was performed before (T0) and after one month of the DAA therapy (T1). MiRNAs discriminating HCC+ and HCC− patients were validated in 60 samples by means of RT-qPCR. We estimated the time-averaged difference of a given miRNA between HCC+ and HCC− patients using a bootstrapped random-effect generalized least square regression model (RE-GLS). At T0, miR-1207-5p, miR-1275, miR-3197, miR-4443, miR-3178, miR-483-5p, miR-4706, miR-4793-3p and miR-1246 discriminated HCC+ from HCC− patients (p < 0.05). At T1, only miR-1180-3p, miR-1228-3p, miR-4329 and miR-4484 (p < 0.05) discriminated HCC+ from HCC− patients. The subsequent validation phase identified miR-3197 as changing with both disease and time. Our results suggest that patients might be already committed to HCC occurrence before DAA therapy. MiR-3197 shows some potential for the identification of patients at risk of HCC during DAA treatments. MDPI 2019-11-11 /pmc/articles/PMC6895878/ /pubmed/31717959 http://dx.doi.org/10.3390/cancers11111773 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
Pascut, Devis
Cavalletto, Luisa
Pratama, Muhammad Yogi
Bresolin, Silvia
Trentin, Luca
Basso, Giuseppe
Bedogni, Giorgio
Tiribelli, Claudio
Chemello, Liliana
Serum miRNA Are Promising Biomarkers for the Detection of Early Hepatocellular Carcinoma after Treatment with Direct-Acting Antivirals
title Serum miRNA Are Promising Biomarkers for the Detection of Early Hepatocellular Carcinoma after Treatment with Direct-Acting Antivirals
title_full Serum miRNA Are Promising Biomarkers for the Detection of Early Hepatocellular Carcinoma after Treatment with Direct-Acting Antivirals
title_fullStr Serum miRNA Are Promising Biomarkers for the Detection of Early Hepatocellular Carcinoma after Treatment with Direct-Acting Antivirals
title_full_unstemmed Serum miRNA Are Promising Biomarkers for the Detection of Early Hepatocellular Carcinoma after Treatment with Direct-Acting Antivirals
title_short Serum miRNA Are Promising Biomarkers for the Detection of Early Hepatocellular Carcinoma after Treatment with Direct-Acting Antivirals
title_sort serum mirna are promising biomarkers for the detection of early hepatocellular carcinoma after treatment with direct-acting antivirals
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895878/
https://www.ncbi.nlm.nih.gov/pubmed/31717959
http://dx.doi.org/10.3390/cancers11111773
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