دورية أكاديمية
High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype
| العنوان: | High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype |
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| المؤلفون: | Golob-Schwarzi, Nicole, Bettermann, Kira, Mehta, Anita Kuldeep, Kessler, Sonja M., Unterluggauer, Julia, Krassnig, Stefanie, Kojima, Kensuke, Chen, Xintong, Hoshida, Yujin, Bardeesy, Nabeel M., Mueller, Heimo, Svendova, Vendula, Schimek, Michael G., Diwoky, Clemens, Lipfert, Alexandra, Mahajan, Vineet, Stumptner, Cornelia, Thueringer, Andrea, Froehlich, Leopold F., Stojakovic, Tatjana, Nilsson, Peter, Kolbe, Thomas, Ruelicke, Thomas, Magin, Thomas M., Strnad, Pavel, Kiemer, Alexandra K., Moriggl, Richard, Haybaeck, Johannes |
| بيانات النشر: | Linköpings universitet, Kemi Linköpings universitet, Tekniska fakulteten Med Univ Graz, Austria; Ctr Biomaker Res Med, Austria Med Univ Graz, Austria Med Univ Graz, Austria; Dana Farber Canc Inst, MA 02215 USA Med Univ Graz, Austria; Saarland Univ, Germany Univ Texas Southwestern Med Ctr Dallas, TX 75390 USA Harvard Med Sch, MA USA Graz Univ Technol, Austria; Karl Franzens Univ Graz, Austria Graz Univ Technol, Austria Med Univ Graz, Austria; Univ Munster, Germany Univ Vet Med Vienna, Austria; Univ Bodenkultur Wien, Austria Univ Vet Med Vienna, Austria Univ Leipzig, Germany Univ Hosp RWTH Aachen, Germany Ctr Biomaker Res Med, Austria Univ Vet Med Vienna, Austria; Ludwig Bolzmann Inst Canc Res, Austria; Med Univ Vienna, Austria Med Univ Graz, Austria; Otto von Guericke Univ, Germany ELSEVIER SCIENCE INC |
| سنة النشر: | 2019 |
| المجموعة: | Linköping University Electronic Press (LiU E-Press) |
| مصطلحات موضوعية: | Cell and Molecular Biology, Cell- och molekylärbiologi |
| الوصف: | 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. ; 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 |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Translational Oncology, 1944-7124, 2019, 12:2, s. 256-268; http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-154092Test; PMID 30439626; ISI:000455497000008 |
| DOI: | 10.1016/j.tranon.2018.10.010 |
| الإتاحة: | https://doi.org/10.1016/j.tranon.2018.10.010Test http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-154092Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.F65506DF |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.tranon.2018.10.010 |
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