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Immunopositivity for Histone MacroH2A1 Isoforms Marks Steatosis-Associated Hepatocellular Carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Prevention and risk reduction are important and the identification of specific biomarkers for early diagnosis of HCC represents an active field of research. Increasing evidence indicates that fat accumulation in...

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Autores principales: Rappa, Francesca, Greco, Azzura, Podrini, Christine, Cappello, Francesco, Foti, Michelangelo, Bourgoin, Lucie, Peyrou, Marion, Marino, Arianna, Scibetta, Nunzia, Williams, Roger, Mazzoccoli, Gianluigi, Federici, Massimo, Pazienza, Valerio, Vinciguerra, Manlio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553099/
https://www.ncbi.nlm.nih.gov/pubmed/23372727
http://dx.doi.org/10.1371/journal.pone.0054458
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author Rappa, Francesca
Greco, Azzura
Podrini, Christine
Cappello, Francesco
Foti, Michelangelo
Bourgoin, Lucie
Peyrou, Marion
Marino, Arianna
Scibetta, Nunzia
Williams, Roger
Mazzoccoli, Gianluigi
Federici, Massimo
Pazienza, Valerio
Vinciguerra, Manlio
author_facet Rappa, Francesca
Greco, Azzura
Podrini, Christine
Cappello, Francesco
Foti, Michelangelo
Bourgoin, Lucie
Peyrou, Marion
Marino, Arianna
Scibetta, Nunzia
Williams, Roger
Mazzoccoli, Gianluigi
Federici, Massimo
Pazienza, Valerio
Vinciguerra, Manlio
author_sort Rappa, Francesca
collection PubMed
description BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Prevention and risk reduction are important and the identification of specific biomarkers for early diagnosis of HCC represents an active field of research. Increasing evidence indicates that fat accumulation in the liver, defined as hepatosteatosis, is an independent and strong risk factor for developing an HCC. MacroH2A1, a histone protein generally associated with the repressed regions of chromosomes, is involved in hepatic lipid metabolism and is present in two alternative spliced isoforms, macroH2A1.1 and macroH2A1.2. These isoforms have been shown to predict lung and colon cancer recurrence but to our knowledge, their role in fatty-liver associated HCC has not been investigated previously. METHODS: We examined macroH2A1.1 and macroH2A1.2 protein expression levels in the liver of two murine models of fat-associated HCC, the high fat diet/diethylnistrosamine (DEN) and the phosphatase and tensin homolog (PTEN) liver specific knock-out (KO) mouse, and in human liver samples of subjects with steatosis or HCC, using immunoblotting and immunohistochemistry. RESULTS: Protein levels for both macroH2A1 isoforms were massively upregulated in HCC, whereas macroH2A1.2 was specifically upregulated in steatosis. In addition, examination of human liver samples showed a significant difference (p<0.01) in number of positive nuclei in HCC (100% of tumor cells positive for either macroH2A1.1 or macroH2A1.2), when compared to steatosis (<2% of hepatocytes positive for either isoform). The steatotic areas flanking the tumors were highly immunopositive for macroH2A1.1 and macroH2A1.2. CONCLUSIONS: These data obtained in mice and humans suggest that both macroH2A1 isoforms may play a role in HCC pathogenesis and moreover may be considered as novel diagnostic markers for human HCC.
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spelling pubmed-35530992013-01-31 Immunopositivity for Histone MacroH2A1 Isoforms Marks Steatosis-Associated Hepatocellular Carcinoma Rappa, Francesca Greco, Azzura Podrini, Christine Cappello, Francesco Foti, Michelangelo Bourgoin, Lucie Peyrou, Marion Marino, Arianna Scibetta, Nunzia Williams, Roger Mazzoccoli, Gianluigi Federici, Massimo Pazienza, Valerio Vinciguerra, Manlio PLoS One Research Article BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Prevention and risk reduction are important and the identification of specific biomarkers for early diagnosis of HCC represents an active field of research. Increasing evidence indicates that fat accumulation in the liver, defined as hepatosteatosis, is an independent and strong risk factor for developing an HCC. MacroH2A1, a histone protein generally associated with the repressed regions of chromosomes, is involved in hepatic lipid metabolism and is present in two alternative spliced isoforms, macroH2A1.1 and macroH2A1.2. These isoforms have been shown to predict lung and colon cancer recurrence but to our knowledge, their role in fatty-liver associated HCC has not been investigated previously. METHODS: We examined macroH2A1.1 and macroH2A1.2 protein expression levels in the liver of two murine models of fat-associated HCC, the high fat diet/diethylnistrosamine (DEN) and the phosphatase and tensin homolog (PTEN) liver specific knock-out (KO) mouse, and in human liver samples of subjects with steatosis or HCC, using immunoblotting and immunohistochemistry. RESULTS: Protein levels for both macroH2A1 isoforms were massively upregulated in HCC, whereas macroH2A1.2 was specifically upregulated in steatosis. In addition, examination of human liver samples showed a significant difference (p<0.01) in number of positive nuclei in HCC (100% of tumor cells positive for either macroH2A1.1 or macroH2A1.2), when compared to steatosis (<2% of hepatocytes positive for either isoform). The steatotic areas flanking the tumors were highly immunopositive for macroH2A1.1 and macroH2A1.2. CONCLUSIONS: These data obtained in mice and humans suggest that both macroH2A1 isoforms may play a role in HCC pathogenesis and moreover may be considered as novel diagnostic markers for human HCC. Public Library of Science 2013-01-23 /pmc/articles/PMC3553099/ /pubmed/23372727 http://dx.doi.org/10.1371/journal.pone.0054458 Text en © 2013 Rappa et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Rappa, Francesca
Greco, Azzura
Podrini, Christine
Cappello, Francesco
Foti, Michelangelo
Bourgoin, Lucie
Peyrou, Marion
Marino, Arianna
Scibetta, Nunzia
Williams, Roger
Mazzoccoli, Gianluigi
Federici, Massimo
Pazienza, Valerio
Vinciguerra, Manlio
Immunopositivity for Histone MacroH2A1 Isoforms Marks Steatosis-Associated Hepatocellular Carcinoma
title Immunopositivity for Histone MacroH2A1 Isoforms Marks Steatosis-Associated Hepatocellular Carcinoma
title_full Immunopositivity for Histone MacroH2A1 Isoforms Marks Steatosis-Associated Hepatocellular Carcinoma
title_fullStr Immunopositivity for Histone MacroH2A1 Isoforms Marks Steatosis-Associated Hepatocellular Carcinoma
title_full_unstemmed Immunopositivity for Histone MacroH2A1 Isoforms Marks Steatosis-Associated Hepatocellular Carcinoma
title_short Immunopositivity for Histone MacroH2A1 Isoforms Marks Steatosis-Associated Hepatocellular Carcinoma
title_sort immunopositivity for histone macroh2a1 isoforms marks steatosis-associated hepatocellular carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553099/
https://www.ncbi.nlm.nih.gov/pubmed/23372727
http://dx.doi.org/10.1371/journal.pone.0054458
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