Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma

doi:10.1038/s41586-019-0987-8

	Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma
	Jiang, Ying 4; Sun, Aihua 4; Zhao, Yang 4,5; Ying, Wantao 4; Sun, Huichuan 6; Yang, Xinrong 1,6; Xing, Baocai 7; Sun, Wei 4; Ren, Liangliang 4; Hu, Bo 1,6
刊名	NATURE
	2019-03-14
卷号	567 期号:7747 页码:257-+
ISSN号	0028-0836
DOI	10.1038/s41586-019-0987-8
通讯作者	Fan, Jia(fan.jia@zs-hospital.sh.cn) ; Qian, Xiaohong(qianxh1@163.com) ; He, Fuchu(hefc@nic.bmi.ac.cn)
英文摘要	Hepatocellular carcinoma is the third leading cause of deaths from cancer worldwide. Infection with the hepatitis B virus is one of the leading risk factors for developing hepatocellular carcinoma, particularly in East Asia(1). Although surgical treatment may be effective in the early stages, the five-year overall rate of survival after developing this cancer is only 50-70%(2). Here, using proteomic and phospho-proteomic profiling, we characterize 110 paired tumour and non-tumour tissues of clinical early-stage hepatocellular carcinoma related to hepatitis B virus infection. Our quantitative proteomic data highlight heterogeneity in early-stage hepatocellular carcinoma: we used this to stratify the cohort into the subtypes S-I, S-II and S-III, each of which has a different clinical outcome. S-III, which is characterized by disrupted cholesterol homeostasis, is associated with the lowest overall rate of survival and the greatest risk of a poor prognosis after first-line surgery. The knockdown of sterol O-acyltransferase 1 (SOAT1)-high expression of which is a signature specific to the S-III subtype-alters the distribution of cellular cholesterol, and effectively suppresses the proliferation and migration of hepatocellular carcinoma. Finally, on the basis of a patient-derived tumour xenograft mouse model of hepatocellular carcinoma, we found that treatment with avasimibe, an inhibitor of SOAT1, markedly reduced the size of tumours that had high levels of SOAT1 expression. The proteomic stratification of early-stage hepatocellular carcinoma presented in this study provides insight into the tumour biology of this cancer, and suggests opportunities for personalized therapies that target it.
资助项目	Chinese Human Proteome Project ; Chinese State Key Projects for Basic Research (973 Program)[2014CBA02001] ; National Key R&D Program of China[2016YFC0902400] ; National Key R&D Program of China[2017YFC0906603] ; National Key R&D Program of China[2018YFA0507502] ; National Key R&D Program of China[2016YFF0101405] ; National Key R&D Program of China[2013ZX10002009] ; National Key R&D Program of China[2009ZX09503-002] ; Program of International ST Cooperation[2014DFB30020,2014DFB30030] ; Program of International ST Cooperation[2014DFB30010] ; Program of International ST Cooperation[2009DFB33070] ; Program of International ST Cooperation[2010DFA31260] ; National Natural Science Foundation of China[81770581] ; National Natural Science Foundation of China[81570526] ; National Natural Science Foundation of China[81772551] ; National Natural Science Foundation of China[81802364] ; National Natural Science Foundation of China[8153077] ; National Natural Science Foundation of China[81672839] ; National Natural Science Foundation of China[81572823] ; National Natural Science Foundation of China[81772578] ; National Natural Science Foundation of China[81123001] ; Beijing Science and Technology Project[Z161100002616036] ; Shanghai 111 Project[B14019] ; Innovation project[16CXZ027]
WOS关键词	GENOMIC CHARACTERIZATION ; GENE ; PATHWAY ; CLASSIFICATION ; FRACTIONATION ; METASTASIS ; ACTIVATION ; ENRICHMENT ; PREDICTION ; MUTATIONS
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000461126600046
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/290296]
专题	中国科学院上海药物研究所
通讯作者	Fan, Jia; Qian, Xiaohong; He, Fuchu
作者单位	1.Fudan Univ, Zhongshan Hosp, Shanghai, Peoples R China 2.BGI Shenzhen, Shenzhen, Peoples R China 3.Fudan Univ, Shanghai Canc Ctr, Shanghai, Peoples R China 4.Beijing Inst Life, State Key Lab Prote, Beijing Proteome Res Ctr, Natl Ctr Prot Sci Beijing, Beijing, Peoples R China 5.Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing, Peoples R China 6.Fudan Univ, Liver Canc Inst, Dept Liver Surg & Transplantat, Shanghai, Peoples R China 7.Peking Univ, Canc Hosp & Inst, Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Beijing, Peoples R China 8.East China Normal Univ, Sch Life Sci, Ctr Bioinformat & Computat Biol, Shanghai, Peoples R China 9.East China Normal Univ, Inst Biomed Sci, Sch Life Sci, Shanghai, Peoples R China 10.Shanghai Acad Sci & Technol, Shanghai Ctr Bioinformat Technol, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Jiang, Ying,Sun, Aihua,Zhao, Yang,et al. Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma[J]. NATURE,2019,567(7747):257-+.
APA	Jiang, Ying.,Sun, Aihua.,Zhao, Yang.,Ying, Wantao.,Sun, Huichuan.,...&Li, Zesong.(2019).Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma.NATURE,567(7747),257-+.
MLA	Jiang, Ying,et al."Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma".NATURE 567.7747(2019):257-+.