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High Keratin 8/18 R...
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Golob-Schwarzi, NicoleMed Univ Graz, Austria; Ctr Biomaker Res Med, Austria
(author)
High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype
- Article/chapterEnglish2019
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ELSEVIER SCIENCE INC,2019
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electronicrdacarrier
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LIBRIS-ID:oai:DiVA.org:liu-154092
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-154092URI
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https://doi.org/10.1016/j.tranon.2018.10.010DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Funding Agencies|Kurt und Senta Herrmann Stiftung; Austrian Genome Programme GEN-AU; DFG [MA1316-15, MA1316-17, MA1316-19, MA1316-21, INST 268/230-1]; German Research Foundation [STR 1095/4-2]; Else Kroner Exzellenzstipendium; Innovative Medicines Initiative Joint Undertaking from the European Unions Seventh Framework Programme (FP7/2007-2013) [115234]; EFPIA companies
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BACKGROUND amp; AIMS: Steatohepatitis (SH) and SH-associated hepatocellular carcinoma (HCC) are of considerable clinical significance. SH is morphologically characterized by steatosis, liver cell ballooning, cytoplasmic aggregates termedMallory-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: Weanalyzed livers of aged Krt18(-/-) mice that spontaneously developed in the majority of cases SH-associated HCC independent of sex. Interestingly, the hepatic lipid profile in Krt18(-/-) mice, which accumulate KRT8, closely resembles human SH lipid profiles and shows that the excess of KRT8 over KRT18 determines the likelihood to develop SH-associated HCC linked with enhanced lipogenesis. RESULTS: Our analysis of the genetic profile of Krt18(-/-) mice with 26 human hepatoma cell lines and with data sets of amp;gt;300 patients with HCC, where Krt18(-/-) gene signatures matched human HCC. Interestingly, a high KRT8/18 ratio is associated with an aggressive HCC phenotype. 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.
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Bettermann, KiraMed Univ Graz, Austria
(author)
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Mehta, Anita KuldeepMed Univ Graz, Austria; Dana Farber Canc Inst, MA 02215 USA
(author)
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Kessler, Sonja M.Med Univ Graz, Austria; Saarland Univ, Germany
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Unterluggauer, JuliaMed Univ Graz, Austria
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Krassnig, StefanieMed Univ Graz, Austria
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Kojima, KensukeUniv Texas Southwestern Med Ctr Dallas, TX 75390 USA
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Chen, XintongUniv Texas Southwestern Med Ctr Dallas, TX 75390 USA
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Hoshida, YujinUniv Texas Southwestern Med Ctr Dallas, TX 75390 USA
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Bardeesy, Nabeel M.Harvard Med Sch, MA USA
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Mueller, HeimoMed Univ Graz, Austria
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Svendova, VendulaMed Univ Graz, Austria
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Schimek, Michael G.Med Univ Graz, Austria
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Diwoky, ClemensGraz Univ Technol, Austria; Karl Franzens Univ Graz, Austria
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Lipfert, AlexandraGraz Univ Technol, Austria
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Mahajan, VineetMed Univ Graz, Austria
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Stumptner, CorneliaMed Univ Graz, Austria
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Thueringer, AndreaMed Univ Graz, Austria
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Froehlich, Leopold F.Med Univ Graz, Austria; Univ Munster, Germany
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Stojakovic, TatjanaMed Univ Graz, Austria
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Nilsson, PeterLinköpings universitet,Kemi,Tekniska fakulteten(Swepub:liu)petni61
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Kolbe, ThomasUniv Vet Med Vienna, Austria; Univ Bodenkultur Wien, Austria
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Ruelicke, ThomasUniv Vet Med Vienna, Austria
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Magin, Thomas M.Univ Leipzig, Germany
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Strnad, PavelUniv Hosp RWTH Aachen, Germany
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Kiemer, Alexandra K.Ctr Biomaker Res Med, Austria
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Moriggl, RichardUniv Vet Med Vienna, Austria; Ludwig Bolzmann Inst Canc Res, Austria; Med Univ Vienna, Austria
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Haybaeck, JohannesMed Univ Graz, Austria; Otto von Guericke Univ, Germany
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Med Univ Graz, Austria; Ctr Biomaker Res Med, AustriaMed Univ Graz, Austria
(creator_code:org_t)
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Kojima, Kensuke
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