Integrated Proteogenomic Characterization of HBV-Related Hepatocellular Carcinoma

Qiang Gao(Fudan University), Hongwen Zhu(Chinese Academy of Sciences), Liangqing Dong(Fudan University), Weiwei Shi(Unimed Medical Institute), Ran Chen(Chinese Academy of Sciences), Zhijian Song(Unimed Medical Institute), Chen Huang(Baylor College of Medicine), Junqiang Li(Unimed Medical Institute), Xiaowei Dong(Unimed Medical Institute), Yanting Zhou(Chinese Academy of Sciences), Qian Liu(Chinese Academy of Sciences), Lijie Ma(Fudan University), Xiaoying Wang(Fudan University), Jian Zhou(Fudan University), Yansheng Liu(Yale Cancer Center), Emily S. Boja(National Cancer Institute), Ana I. Robles(National Cancer Institute), Weiping Ma(Icahn School of Medicine at Mount Sinai), Pei Wang(Icahn School of Medicine at Mount Sinai), Yize Li(James S. McDonnell Foundation), Li Ding(James S. McDonnell Foundation), Bo Wen(Baylor College of Medicine), Bing Zhang(Baylor College of Medicine), Henry Rodriguez(National Cancer Institute), Daming Gao(Chinese Academy of Sciences), Hu Zhou(Chinese Academy of Sciences), Jia Fan(Fudan University)
Cell
October 1, 2019
10.1016/j.cell.2019.08.052
Cited by 1,150Open Access
Full Text

Abstract

We performed the first proteogenomic characterization of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) using paired tumor and adjacent liver tissues from 159 patients. Integrated proteogenomic analyses revealed consistency and discordance among multi-omics, activation status of key signaling pathways, and liver-specific metabolic reprogramming in HBV-related HCC. Proteomic profiling identified three subgroups associated with clinical and molecular attributes including patient survival, tumor thrombus, genetic profile, and the liver-specific proteome. These proteomic subgroups have distinct features in metabolic reprogramming, microenvironment dysregulation, cell proliferation, and potential therapeutics. Two prognostic biomarkers, PYCR2 and ADH1A, related to proteomic subgrouping and involved in HCC metabolic reprogramming, were identified. CTNNB1 and TP53 mutation-associated signaling and metabolic profiles were revealed, among which mutated CTNNB1-associated ALDOA phosphorylation was validated to promote glycolysis and cell proliferation. Our study provides a valuable resource that significantly expands the knowledge of HBV-related HCC and may eventually benefit clinical practice.

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