Integrated Proteogenomic Characterization of HBV-Related Hepatocellular Carcinoma

被引：635

作者：

Gao, Qiang ^{[1
,2
]}

Zhu, Hongwen ^{[3
,4
]}

Dong, Liangqing ^{[1
,2
]}

Shi, Weiwei ^{[5
]}

Chen, Ran ^{[6
,7
]}

Song, Zhijian ^{[5
]}

Huang, Chen ^{[8
]}

Li, Junqiang ^{[5
]}

Dong, Xiaowei ^{[5
]}

Zhou, Yanting ^{[3
,4
]}

Liu, Qian ^{[3
,4
,7
]}

Ma, Lijie ^{[1
,2
]}

Wang, Xiaoying ^{[1
,2
]}

Zhou, Jian ^{[1
,2
,9
]}

Liu, Yansheng ^{[10
]}

Boja, Emily ^{[11
]}

Robles, Ana I. ^{[11
]}

Ma, Weiping ^{[12
]}

Wang, Pei ^{[12
]}

Li, Yize ^{[13
]}

Ding, Li ^{[13
]}

Wen, Bo ^{[8
]}

Zhang, Bing ^{[8
]}

Rodriguez, Henry ^{[11
]}

Gao, Daming ^{[6
,7
]}

Zhou, Hu ^{[3
,4
,7
]}

Fan, Jia ^{[1
,2
,9
]}

机构：

[1] Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Dept Liver Surg & Transplantat, 180 Fenglin Rd, Shanghai 200032, Peoples R China

[2] Minist Educ, Key Lab Carcinogenesis & Canc Invas, 180 Fenglin Rd, Shanghai 200032, Peoples R China

[3] Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China

[4] Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China

[5] OrigiMed, Shanghai 201114, Peoples R China

[6] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Cell Biol, Ctr Excellence Mol Cell Sci, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China

[7] Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China

[8] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Dept Mol & Human Genet, One Baylor Plaza, Houston, TX 77030 USA

[9] Fudan Univ, Inst Biomed Sci, Key Lab Med Epigenet & Metab, Shanghai 200032, Peoples R China

[10] Yale Univ, Sch Med, Dept Pharmacol, Canc Biol Inst, West Haven, CT 06516 USA

[11] NCI, Off Canc Clin Prote Res, Ctr Strateg Sci Initiat, NIH, Bethesda, MD 20892 USA

[12] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA

[13] Washington Univ, Dept Med, McDonnell Genome Inst, Siteman Canc Ctr, St Louis, MO 63108 USA

来源：

CELL | 2019年 / 179卷 / 02期

基金：

中国国家自然科学基金;

关键词：

VITAMIN-A TOXICITY; GROWTH-FACTOR-BETA; SOMATIC MUTATIONS; PIVOTAL ROLE; HEPATITIS-B; HUMAN COLON; EXPRESSION; CANCER; IDENTIFICATION; CLASSIFICATION;

D O I：

10.1016/j.cell.2019.08.052

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：561 / +

页数：39

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