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


Authors: Zheng, J.; Sadot, E.; Vigidal, J. A.; Klimstra, D. S.; Balachandran, V. P.; Kingham, T. P.; Allen, P. J.; D’Angelica, M. I.; DeMatteo, R. P.; Jarnagin, W. R.; Ventura, A.
Article Title: Characterization of hepatocellular adenoma and carcinoma using microRNA profiling and targeted gene sequencing
Abstract: Background 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. Methods 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. Results 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. Conclusions 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 hepato-carcinogenesis and warrant further investigations. © 2018 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Journal Title: PLoS ONE
Volume: 13
Issue: 7
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2018-07-27
Start Page: e0200776
Language: English
DOI: 10.1371/journal.pone.0200776
PROVIDER: scopus
PMCID: PMC6063411
PUBMED: 30052636
DOI/URL:
Notes: Joana A. Vidigal's name is misspelled on the original publication -- Article -- Export Date: 1 October 2018 -- Source: Scopus
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MSK Authors
  1. Ronald P DeMatteo
    597 DeMatteo
  2. David S Klimstra
    843 Klimstra
  3. Peter Allen
    436 Allen
  4. William R Jarnagin
    583 Jarnagin
  5. T Peter Kingham
    281 Kingham
  6. Andrea Ventura
    36 Ventura
  7. Eran Sadot
    35 Sadot
  8. Jian Ying Zheng
    14 Zheng