PT  - JOURNAL ARTICLE
AU  - Charlotte K Y Ng
AU  - Eva Dazert
AU  - Tuyana Boldanova
AU  - Mairene Coto-Llerena
AU  - Sandro Nuciforo
AU  - Caner Ercan
AU  - Aleksei Suslov
AU  - Marie-Anne Meier
AU  - Thomas Bock
AU  - Alexander Schmidt
AU  - Sylvia Ketterer
AU  - Xueya Wang
AU  - Stefan Wieland
AU  - Matthias S Matter
AU  - Marco Colombi
AU  - Salvatore Piscuoglio
AU  - Luigi M Terracciano
AU  - Michael N Hall
AU  - Markus H Heim
TI  - Proteogenomic characterization of hepatocellular carcinoma
AID  - 10.1101/2021.03.05.434147
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.05.434147
4099  - http://biorxiv.org/content/early/2021/03/07/2021.03.05.434147.short
4100  - http://biorxiv.org/content/early/2021/03/07/2021.03.05.434147.full
AB  - We performed a proteogenomic analysis of hepatocellular carcinomas (HCCs) across clinical stages and etiologies. We identified pathways differentially regulated on the genomic, transcriptomic, proteomic and phosphoproteomic levels. These pathways are involved in the organization of cellular components, cell cycle control, signaling pathways, transcriptional and translational control and metabolism. Analyses of CNA-mRNA and mRNA-protein correlations identified candidate driver genes involved in epithelial-to-mesenchymal transition, the Wnt-β-catenin pathway, transcriptional control, cholesterol biosynthesis and sphingolipid metabolism. The activity of targetable kinases aurora kinase A and CDKs was upregulated. We found that CTNNB1 mutations are associated with altered phosphorylation of proteins involved in actin filament organization, whereas TP53 mutations are associated with elevated CDK1/2/5 activity and altered phosphorylation of proteins involved in lipid and mRNA metabolism. Integrative clustering identified HCC subgroups with distinct regulation of biological processes, metabolic reprogramming and kinase activation. Our analysis provides insights into the molecular processes underlying HCCs.Competing Interest StatementThe authors have declared no competing interest.