Characterization of hepatocellular adenoma and carcinoma using microRNA profiling and targeted gene sequencing.

<h4>Background</h4>Hepatocellular adenomas (HCA) are benign liver tumors that may transform into hepatocellular carcinoma (HCC), but the molecular drivers of this transformation remain ill-defined. This study evaluates the molecular changes in HCA and HCC and in comparison to their adjac...

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Main Authors: Jian Zheng, Eran Sadot, Joana A Vigidal, David S Klimstra, Vinod P Balachandran, T Peter Kingham, Peter J Allen, Michael I D'Angelica, Ronald P DeMatteo, William R Jarnagin, Andrea Ventura
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0200776&type=printable
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author Jian Zheng
Eran Sadot
Joana A Vigidal
David S Klimstra
Vinod P Balachandran
T Peter Kingham
Peter J Allen
Michael I D'Angelica
Ronald P DeMatteo
William R Jarnagin
Andrea Ventura
author_facet Jian Zheng
Eran Sadot
Joana A Vigidal
David S Klimstra
Vinod P Balachandran
T Peter Kingham
Peter J Allen
Michael I D'Angelica
Ronald P DeMatteo
William R Jarnagin
Andrea Ventura
author_sort Jian Zheng
collection DOAJ
description <h4>Background</h4>Hepatocellular adenomas (HCA) are benign liver tumors that may transform into hepatocellular carcinoma (HCC), but the molecular drivers of this transformation remain ill-defined. This study evaluates the molecular changes in HCA and HCC and in comparison to their adjacent non-neoplastic liver.<h4>Methods</h4>11 patients with HCA and 10 patients with HCC without underlying hepatitis or cirrhosis were included in this pilot study. Tumor and non-tumor liver tissues were selected for immunohistochemical staining, small RNA sequencing, and targeted gene sequencing. We compared microRNA expressions and mutations between HCA and HCC and non-neoplastic liver.<h4>Results</h4>HCA were classified as inflammatory (n = 6), steatotic (n = 4), or β-catenin activated (n = 1) subtypes. MicroRNA profile of all 3 HCA subtypes clustered between that of normal liver and HCC in principal component analysis. In both HCA and HCC, miR-200a, miR-429, and miR-490-3p were significantly downregulated compared to normal liver, whereas miR-452, miR-766, and miR-1180 were significantly upregulated. In addition, compared to HCA, HCC had significantly higher expression of members of the chromosome 19 miRNA cluster (C19MC), including miR-515-5p, miR-517a, miR-518b, and miR-520c-3p.<h4>Conclusions</h4>This study indicates that while there are significant differences in the molecular profile between HCA and HCC, several miRNAs are similarly deregulated in HCA and HCC compared to adjacent normal liver. These results may provide insights into the drivers of hepatocarcinogenesis and warrant further investigations.
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spelling doaj-art-08842624098d44c8a17a5710b39ff61d2025-08-20T02:45:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01137e020077610.1371/journal.pone.0200776Characterization of hepatocellular adenoma and carcinoma using microRNA profiling and targeted gene sequencing.Jian ZhengEran SadotJoana A VigidalDavid S KlimstraVinod P BalachandranT Peter KinghamPeter J AllenMichael I D'AngelicaRonald P DeMatteoWilliam R JarnaginAndrea Ventura<h4>Background</h4>Hepatocellular adenomas (HCA) are benign liver tumors that may transform into hepatocellular carcinoma (HCC), but the molecular drivers of this transformation remain ill-defined. This study evaluates the molecular changes in HCA and HCC and in comparison to their adjacent non-neoplastic liver.<h4>Methods</h4>11 patients with HCA and 10 patients with HCC without underlying hepatitis or cirrhosis were included in this pilot study. Tumor and non-tumor liver tissues were selected for immunohistochemical staining, small RNA sequencing, and targeted gene sequencing. We compared microRNA expressions and mutations between HCA and HCC and non-neoplastic liver.<h4>Results</h4>HCA were classified as inflammatory (n = 6), steatotic (n = 4), or β-catenin activated (n = 1) subtypes. MicroRNA profile of all 3 HCA subtypes clustered between that of normal liver and HCC in principal component analysis. In both HCA and HCC, miR-200a, miR-429, and miR-490-3p were significantly downregulated compared to normal liver, whereas miR-452, miR-766, and miR-1180 were significantly upregulated. In addition, compared to HCA, HCC had significantly higher expression of members of the chromosome 19 miRNA cluster (C19MC), including miR-515-5p, miR-517a, miR-518b, and miR-520c-3p.<h4>Conclusions</h4>This study indicates that while there are significant differences in the molecular profile between HCA and HCC, several miRNAs are similarly deregulated in HCA and HCC compared to adjacent normal liver. These results may provide insights into the drivers of hepatocarcinogenesis and warrant further investigations.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0200776&type=printable
spellingShingle Jian Zheng
Eran Sadot
Joana A Vigidal
David S Klimstra
Vinod P Balachandran
T Peter Kingham
Peter J Allen
Michael I D'Angelica
Ronald P DeMatteo
William R Jarnagin
Andrea Ventura
Characterization of hepatocellular adenoma and carcinoma using microRNA profiling and targeted gene sequencing.
PLoS ONE
title Characterization of hepatocellular adenoma and carcinoma using microRNA profiling and targeted gene sequencing.
title_full Characterization of hepatocellular adenoma and carcinoma using microRNA profiling and targeted gene sequencing.
title_fullStr Characterization of hepatocellular adenoma and carcinoma using microRNA profiling and targeted gene sequencing.
title_full_unstemmed Characterization of hepatocellular adenoma and carcinoma using microRNA profiling and targeted gene sequencing.
title_short Characterization of hepatocellular adenoma and carcinoma using microRNA profiling and targeted gene sequencing.
title_sort characterization of hepatocellular adenoma and carcinoma using microrna profiling and targeted gene sequencing
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0200776&type=printable
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