High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype.


Journal

Translational oncology
ISSN: 1936-5233
Titre abrégé: Transl Oncol
Pays: United States
ID NLM: 101472619

Informations de publication

Date de publication:
Feb 2019
Historique:
received: 06 09 2018
revised: 22 10 2018
accepted: 25 10 2018
pubmed: 16 11 2018
medline: 16 11 2018
entrez: 16 11 2018
Statut: ppublish

Résumé

Steatohepatitis (SH) and SH-associated hepatocellular carcinoma (HCC) are of considerable clinical significance. SH is morphologically characterized by steatosis, liver cell ballooning, cytoplasmic aggregates termed Mallory-Denk bodies (MDBs), inflammation, and fibrosis at late stage. Disturbance of the keratin cytoskeleton and aggregation of keratins (KRTs) are essential for MDB formation. We analyzed livers of aged Krt18 Our analysis of the genetic profile of Krt18 We can prove that intermediate filaments and their binding partners are tightly linked to hepatic lipid metabolism and to hepatocarcinogenesis. We suggest KRT8/18 ratio as a novel HCC biomarker for HCC.

Sections du résumé

BACKGROUND & AIMS OBJECTIVE
Steatohepatitis (SH) and SH-associated hepatocellular carcinoma (HCC) are of considerable clinical significance. SH is morphologically characterized by steatosis, liver cell ballooning, cytoplasmic aggregates termed Mallory-Denk bodies (MDBs), inflammation, and fibrosis at late stage. Disturbance of the keratin cytoskeleton and aggregation of keratins (KRTs) are essential for MDB formation.
METHODS METHODS
We analyzed livers of aged Krt18
RESULTS RESULTS
Our analysis of the genetic profile of Krt18
CONCLUSIONS CONCLUSIONS
We can prove that intermediate filaments and their binding partners are tightly linked to hepatic lipid metabolism and to hepatocarcinogenesis. We suggest KRT8/18 ratio as a novel HCC biomarker for HCC.

Identifiants

pubmed: 30439626
pii: S1936-5233(18)30439-X
doi: 10.1016/j.tranon.2018.10.010
pmc: PMC6234703
pii:
doi:

Types de publication

Journal Article

Langues

eng

Pagination

256-268

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK099558
Pays : United States

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Références

Lancet. 2018 Mar 31;391(10127):1301-1314
pubmed: 29307467
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Lancet. 2012 Mar 31;379(9822):1245-55
pubmed: 22353262
J Hepatol. 2013 Oct;59(4):842-58
pubmed: 23714158
Ann Epidemiol. 2007 Nov;17(11):863-9
pubmed: 17728149
Histochem Cell Biol. 2008 Jun;129(6):735-49
pubmed: 18443813
Annu Rev Med. 2010;61:317-28
pubmed: 20059340
Cancer Res. 2010 Dec 15;70(24):10202-12
pubmed: 21159642
Dig Liver Dis. 2010 Jul;42 Suppl 3:S235-41
pubmed: 20547309
Lab Invest. 2012 Jun;92(6):857-67
pubmed: 22449798
J Hepatol. 2000 Apr;32(4):689-702
pubmed: 10782920
Nutr Rev. 2007 Jun;65(6 Pt 2):S57-63
pubmed: 17605315
Gut Liver. 2012 Apr;6(2):149-71
pubmed: 22570745
Gastroenterology. 2013 Jul;145(1):176-187
pubmed: 23567350
Cancer Res. 2008 Aug 15;68(16):6779-88
pubmed: 18701503
Hepatology. 2017 Mar;65(3):836-852
pubmed: 27862118
Gastroenterology. 2011 Sep;141(3):1080-1090.e1-7
pubmed: 21699779
Clin Liver Dis. 2012 Aug;16(3):505-24
pubmed: 22824478
Hepatology. 2010 Jun;51(6):1972-8
pubmed: 20209604
Bioinformatics. 2009 Mar 15;25(6):703-13
pubmed: 19147666
J Hepatol. 2008 May;48(5):821-8
pubmed: 18329127
Lancet. 2012 Dec 15;380(9859):2095-128
pubmed: 23245604
J Gastroenterol Hepatol. 2016 May;31(5):936-44
pubmed: 26667191
Gastroenterology. 2011 May;140(5):1501-12.e2
pubmed: 21320499
Exp Cell Res. 2007 Jun 10;313(10):2033-49
pubmed: 17531973
World J Gastroenterol. 2017 Sep 28;23(36):6571-6592
pubmed: 29085206
Gastroenterology. 2005 Sep;129(3):885-93
pubmed: 16143128
Dig Liver Dis. 2010 Jul;42 Suppl 3:S264-72
pubmed: 20547313
Int J Mol Sci. 2016 Jan 13;17(1):null
pubmed: 26771611
Cancer Res. 2009 Sep 15;69(18):7385-92
pubmed: 19723656
Hepatology. 2006 Jun;43(6):1354-63
pubmed: 16729313
Hepatology. 2016 Mar;63(3):827-38
pubmed: 26599351
J Cell Biol. 2000 Oct 30;151(3):563-72
pubmed: 11062258
Bioinformatics. 2004 Dec 12;20(18):3413-22
pubmed: 15381628
Expert Rev Gastroenterol Hepatol. 2018 Apr;12(4):351-367
pubmed: 29224471
Proc Nutr Soc. 2010 May;69(2):211-20
pubmed: 20158939
Curr Opin Cell Biol. 2015 Feb;32:73-81
pubmed: 25599598
Dig Liver Dis. 2017 May;49(5):471-483
pubmed: 28215516
Hepatology. 2001 Mar;33(3):676-91
pubmed: 11230749
Oncotarget. 2016 Nov 8;7(45):73309-73322
pubmed: 27689336
Semin Liver Dis. 2010 Feb;30(1):35-51
pubmed: 20175032
Hepatology. 2002 May;35(5):1134-43
pubmed: 11981763
J Clin Invest. 2004 Jul;114(2):147-52
pubmed: 15254578
Clin Gastroenterol Hepatol. 2012 Aug;10(8):837-58
pubmed: 22446927
Cancer Control. 2017 Jul-Sep;24(3):1073274817729245
pubmed: 28975830
Biochim Biophys Acta. 2011 Aug;1812(8):1007-22
pubmed: 21382489
Science. 2011 Jun 24;332(6037):1519-23
pubmed: 21700865

Auteurs

Nicole Golob-Schwarzl (N)

Institute of Pathology, Medical University of Graz, Graz, Austria; Center for Biomarker Research in Medicine, Graz, Austria.

Kira Bettermann (K)

Institute of Pathology, Medical University of Graz, Graz, Austria.

Anita Kuldeep Mehta (AK)

Institute of Pathology, Medical University of Graz, Graz, Austria; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.

Sonja M Kessler (SM)

Institute of Pathology, Medical University of Graz, Graz, Austria; Department of Pharmacy, Pharmaceutical Biology, Saarland University, Saarbrücken, Germany.

Julia Unterluggauer (J)

Institute of Pathology, Medical University of Graz, Graz, Austria.

Stefanie Krassnig (S)

Institute of Pathology, Medical University of Graz, Graz, Austria.

Kensuke Kojima (K)

Liver Tumor Translational Research Program, University of Texas Southwestern Medical Center, Dallas, USA.

Xintong Chen (X)

Liver Tumor Translational Research Program, University of Texas Southwestern Medical Center, Dallas, USA.

Yujin Hoshida (Y)

Liver Tumor Translational Research Program, University of Texas Southwestern Medical Center, Dallas, USA.

Nabeel M Bardeesy (NM)

Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, USA.

Heimo Müller (H)

Institute of Pathology, Medical University of Graz, Graz, Austria.

Vendula Svendova (V)

Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.

Michael G Schimek (MG)

Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.

Clemens Diwoky (C)

Institute of Medical Engineering, Graz University of Technology, Graz, Austria; Institute of Molecular Biosciences, University of Graz, Graz, Austria.

Alexandra Lipfert (A)

Institute of Medical Engineering, Graz University of Technology, Graz, Austria.

Vineet Mahajan (V)

Institute of Pathology, Medical University of Graz, Graz, Austria.

Cornelia Stumptner (C)

Institute of Pathology, Medical University of Graz, Graz, Austria.

Andrea Thüringer (A)

Institute of Pathology, Medical University of Graz, Graz, Austria.

Leopold F Fröhlich (LF)

Institute of Pathology, Medical University of Graz, Graz, Austria; AG VABOS, Department of Cranio-Maxillofacial Surgery, Univerity of Muenster, Germany.

Tatjana Stojakovic (T)

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.

K P R Nilsson (KPR)

Department of Chemistry, Linköping University, Linköping, Sweden.

Thomas Kolbe (T)

Biomodels Austria (Biat), University of Veterinary Medicine Vienna, Vienna, Austria; Department IFA-Tulln, University for Natural Resources and Applied Life Sciences Vienna, Vienna, Austria.

Thomas Rülicke (T)

Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna, Vienna, Austria.

Thomas M Magin (TM)

Institute of Biology, University of Leipzig, Leipzig, Germany.

Pavel Strnad (P)

Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany.

Alexandra K Kiemer (AK)

Center for Biomarker Research in Medicine, Graz, Austria.

Richard Moriggl (R)

Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria; Ludwig Bolzmann Institute of Cancer Research, Vienna, Austria; Medical University Vienna, Vienna, Austria.

Johannes Haybaeck (J)

Institute of Pathology, Medical University of Graz, Graz, Austria; Department of Pathology, Medical Faculty, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany. Electronic address: Johannes.haybaeck@med.ovgu.de.

Classifications MeSH