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Integrative proteogenomic characterization of hepatocellular carcinoma across etiologies and stages

Author

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  • Charlotte K. Y. Ng

    (University Hospital Basel, University of Basel
    University Hospital Basel, University of Basel
    University of Bern
    SIB Swiss Institute of Bioinformatics)

  • Eva Dazert

    (University of Basel)

  • Tuyana Boldanova

    (University Hospital Basel, University of Basel
    University Hospital Basel)

  • Mairene Coto-Llerena

    (University Hospital Basel, University of Basel
    University Hospital Basel, University of Basel)

  • Sandro Nuciforo

    (University Hospital Basel, University of Basel)

  • Caner Ercan

    (University Hospital Basel, University of Basel)

  • Aleksei Suslov

    (University Hospital Basel, University of Basel)

  • Marie-Anne Meier

    (University Hospital Basel, University of Basel)

  • Thomas Bock

    (University of Basel)

  • Alexander Schmidt

    (University of Basel)

  • Sylvia Ketterer

    (University Hospital Basel, University of Basel)

  • Xueya Wang

    (University Hospital Basel, University of Basel)

  • Stefan Wieland

    (University Hospital Basel, University of Basel)

  • Matthias S. Matter

    (University Hospital Basel, University of Basel)

  • Marco Colombi

    (University of Basel)

  • Salvatore Piscuoglio

    (University Hospital Basel, University of Basel
    University Hospital Basel, University of Basel)

  • Luigi M. Terracciano

    (University Hospital Basel, University of Basel
    Humanitas Clinical and Research Center, IRCCS
    Humanitas University)

  • Michael N. Hall

    (University of Basel)

  • Markus H. Heim

    (University Hospital Basel, University of Basel
    University Hospital Basel)

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.

Suggested Citation

  • Charlotte K. Y. Ng & Eva Dazert & Tuyana Boldanova & Mairene Coto-Llerena & Sandro Nuciforo & Caner Ercan & Aleksei Suslov & Marie-Anne Meier & Thomas Bock & Alexander Schmidt & Sylvia Ketterer & Xuey, 2022. "Integrative proteogenomic characterization of hepatocellular carcinoma across etiologies and stages," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29960-8
    DOI: 10.1038/s41467-022-29960-8
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