Journal Article

Integrative proteogenomic characterization of hepatocellular carcinoma across etiologies and stages

Ng, Charlotte K. Y., Dazert, Eva, Hall, Michael N., Suslov, Aleksei, Wieland, Stefan, Meier, Marie-Anne, Wang, Xueya, Matter, Matthias S., Colombi, Marco, Ketterer, Sylvia, Terracciano, Luigi M., Heim, Markus H., Bock, Thomas, Ercan, Caner, Schmidt, Alexander, Piscuoglio, Salvatore, Boldanova, Tuyana, Nuciforo, Sandro, Coto-Llerena, Mairene

2022

Overview

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. Proteogenomic analyses of hepatocellular carcinomas (HCC) have focused on early-stage, HBV-associated tumours and lacked information about the phosphoproteome. Here, the authors present a comprehensive HCC proteogenomics and phosphoproteomics study in patient samples from multiple etiologies and stages.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/91 / 45/23 / 631/337/475 / 631/45/612/1246 / 631/67/1504/1610/4029 / 631/67/2329 / 631/67/69 / 82/58 / Actin / AKT protein / Aurora kinase / beta Catenin - metabolism / Biological activity / Carcinoma, Hepatocellular - metabolism / Cell cycle / Copy number / DNA damage / Etiology / Hepatocellular carcinoma / Humanities and Social Sciences / Humans / Kinases / Lipid metabolism / Lipids / Liver cancer / Liver Neoplasms - metabolism / Mesenchyme / Metabolic rate / Metabolism / multidisciplinary / Mutation / p53 Protein / Phosphorylation / Proteogenomics / Proteomes / Proteomics / Science / Science (multidisciplinary) / Signal transduction / Subgroups / TOR protein / Transcription / Transcriptomics / Tumors / Wnt protein / β-Catenin