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Integrative proteogenomic characterization of hepatocellular carcinoma across etiologies and stages

Ng, Charlotte K. Y. and Dazert, Eva and Boldanova, Tuyana and Coto-Llerena, Mairene and Nuciforo, Sandro and Ercan, Caner and Suslov, Aleksei and Meier, Marie-Anne and Bock, Thomas and Schmidt, Alexander and Ketterer, Sylvia and Wang, Xueya and Wieland, Stefan and Matter, Matthias S. and Colombi, Marco and Piscuoglio, Salvatore and Terracciano, Luigi M. and Hall, Michael N. and Heim, Markus H.. (2022) Integrative proteogenomic characterization of hepatocellular carcinoma across etiologies and stages. Nature Communications, 13. p. 2436.

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Official URL: https://edoc.unibas.ch/88614/

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Abstract

Proteogenomic analyses of hepatocellular carcinomas (HCC) have focused on early-stage, HBV-associated HCCs. Here we present an integrated proteogenomic analysis of HCCs across clinical stages and etiologies. Pathways related to cell cycle, transcriptional and translational control, signaling transduction, and metabolism are dysregulated and differentially regulated on the genomic, transcriptomic, proteomic and phosphoproteomic levels. We describe candidate copy number-driven driver genes involved in epithelial-to-mesenchymal transition, the Wnt-β-catenin, AKT/mTOR and Notch pathways, cell cycle and DNA damage regulation. The targetable aurora kinase A and CDKs are upregulated. CTNNB1 and TP53 mutations are associated with altered protein phosphorylation related to actin filament organization and lipid metabolism, respectively. Integrative proteogenomic clusters show that HCC constitutes heterogeneous subgroups with distinct regulation of biological processes, metabolic reprogramming and kinase activation. Our study provides a comprehensive overview of the proteomic and phophoproteomic landscapes of HCCs, revealing the major pathways altered in the (phospho)proteome.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
UniBasel Contributors:Hall, Michael N.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Research
e-ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:20 Jun 2022 15:22
Deposited On:19 Jun 2022 16:09

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