六氯环己烷
生物
PI3K/AKT/mTOR通路
蛋白质组
转录组
Wnt信号通路
蛋白质基因组学
小桶
信号转导
蛋白质组学
细胞周期
癌症研究
蛋白激酶B
计算生物学
细胞生物学
基诺美
肝细胞癌
基因
生物信息学
基因表达
遗传学
作者
Charlotte K.Y. Ng,Eva Dazert,Tuyana Boldanova,Mairene Coto‐Llerena,Sandro Nuciforo,Caner Ercan,Aleksei Suslov,Mario Meier,Thomas Bock,Alexander Schmidt,Sylvia Ketterer,Xueya Wang,Stefan Wieland,Matthias S. Matter,Marco Colombi,Salvatore Piscuoglio,Luigi Terracciano,Michael N. Hall,Markus H. Heim
标识
DOI:10.1038/s41467-022-29960-8
摘要
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.
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