Ng, Charlotte K Y; Dazert, Eva; Boldanova, Tuyana; Coto-Llerena, Mairene; Nuciforo, Sandro; Ercan, Caner; Suslov, Aleksei; Meier, Marie-Anne; Bock, Thomas; Schmidt, Alexander; Ketterer, Sylvia; Wang, Xueya; Wieland, Stefan; Matter, Matthias S; Colombi, Marco; Piscuoglio, Salvatore; Terracciano, Luigi M; Hall, Michael N; Heim, Markus H (2022). Integrative proteogenomic characterization of hepatocellular carcinoma across etiologies and stages. Nature Communications, 13(1), p. 2436. Springer Nature 10.1038/s41467-022-29960-8
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) |
UniBE Contributor: |
Ng, Kiu Yan Charlotte |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2041-1723 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
06 May 2022 12:25 |
Last Modified: |
05 Dec 2022 16:19 |
Publisher DOI: |
10.1038/s41467-022-29960-8 |
PubMed ID: |
35508466 |
BORIS DOI: |
10.48350/169779 |
URI: |
https://boris.unibe.ch/id/eprint/169779 |
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