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p Proteogenomic characterization identifies clinically relevant subgroups of intrahepatic cholangiocarcinoma

文献类型：期刊论文

作者Dong, Liangqing12; Lu, Dayun13,14,15; Chen, Ran15,16; Lin, Youpei12; Zhu, Hongwen13,14; Zhang, Zhou17; Cai, Shangli17; Cui, Peng17; Song, Guohe12; Rao, Dongning12
刊名CANCER CELL
出版日期2022-01-10
卷号40期号:1页码:70-+
ISSN号1535-6108
DOI10.1016/j.ccell.2021.12.006
通讯作者Gao, Qiang(gaoqiang@fudan.edu.cn) ; Gao, Daming(dgao@sibcb.ac.cn) ; Zhou, Hu(zhouhu@simm.ac.cr) ; Fan, Jia(fan.jia@zs-hospital.sh.cn)
英文摘要We performed proteogenomic characterization of intrahepatic cholangiocarcinoma (iCCA) using paired tumor and adjacent liver tissues from 262 patients. Integrated proteogenomic analyses prioritized genetic aberrations and revealed hallmarks of iCCA pathogenesis. Aflatoxin signature was associated with tumor initiation, proliferation, and immune suppression. Mutation-associated signaling profiles revealed that TP53 and KRAS co mutations may contribute to iCCA metastasis via the integrin-FAK-SRC pathway. FGFR2 fusions activated the Rho GTPase pathway and could be a potential source of neoantigens. Proteomic profiling identified four patient subgroups (S1-S4) with subgroup-specific biomarkers. These proteomic subgroups had distinct features in prognosis, genetic alterations, microenvironment dysregulation, tumor microbiota composition, and potential therapeutics. SLC16A3 and HKDC1 were further identified as potential prognostic biomarkers associated with metabolic reprogramming of iCCA cells. This study provides a valuable resource for researchers and clinicians to further identify molecular pathogenesis and therapeutic opportunities in iCCA.
WOS关键词THERAPEUTIC TARGETS ; ENRICHMENT ANALYSIS ; PANCREATIC-CANCER ; POOR-PROGNOSIS ; R PACKAGE ; GENE ; EXPRESSION ; GENOME ; IMMUNOTHERAPY ; INHIBITION
资助项目National Key Research and Development Program of China[2020YFE0202200] ; National Key Research and Development Program of China[2020YFA0803203] ; National Key Research and Development Program of China[2017YFC1700200] ; National Key Research and Development Program of China[2020YFA0509000] ; National Key Research and Development Program of China[2019YFA0802102] ; National Natural Science Foundation of China[82130077] ; National Natural Science Foundation of China[81961128025] ; National Natural Science Foundation of China[91859105] ; National Natural Science Foundation of China[81925029] ; National Natural Science Foundation of China[91853130] ; National Natural Science Foundation of China[81790253] ; National Natural Science Foundation of China[82002514] ; Science and Technology Commission of Shanghai Municipality[21JC1410100] ; Science and Technology Commission of Shanghai Municipality[20JC1418900] ; Science and Technology Commission of Shanghai Municipality[20XD1424900] ; Science and Technology Commission of Shanghai Municipality[20YF1407400] ; Shanghai Municipal Health Commission Collaborative Innovation Cluster Project[2019CXJQ02] ; Shanghai Municipal Science and Technology Major Project ; ChineseAcademy ofScience, Fudan University ; US National Cancer Institute's Office of Cancer Clinical Proteomics Research ; US National Cancer Institute's International Cancer Proteogenome Consortium(ICPC) ; StrategicPriorityResearch Programof theChinese Academy of Sciences[XDB19020203] ; [YSBR-014]
WOS研究方向Oncology ; Cell Biology
语种英语
WOS记录号WOS:000744691500013
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/300507]  
专题中国科学院上海药物研究所
通讯作者Gao, Qiang; Gao, Daming; Zhou, Hu; Fan, Jia
作者单位1.Fudan Univ, Inst Biomed Sci, Key Lab Med Epigenet & Metab, Shanghai 200032, Peoples R China
2.Univ Ottawa, Fac Med, Ottawa Inst Syst Biol, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada
3.Shanghai Inst Mat Med Univ Ottawa Joint Res Ctr S, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
4.Shanghai Jiao Tong Univ, Collaborat Innovat Ctr Brain Sci, Bio X Inst, Minist Educ,Key Lab Genet Dev & Neuropsychiat Dis, Shanghai, Peoples R China
5.Washington Univ, Siteman Canc Ctr, McDonnell Genome Inst, Dept Med, St Louis, MO 63108 USA
6.Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA
7.Baylor Coll Med, Lester & Sue Smith Breast Ctr, Dept Mol & Human Genet, One Baylor Plaza, Houston, TX 77030 USA
8.NCI, Off Canc Clin Prote Res, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA
9.Fudan Univ, State Key Lab Genet Engn, Shanghai 200433, Peoples R China
10.Univ Chinese Acad Sci, Sch Life Sci, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China
推荐引用方式
GB/T 7714		 Dong, Liangqing,Lu, Dayun,Chen, Ran,et al. p Proteogenomic characterization identifies clinically relevant subgroups of intrahepatic cholangiocarcinoma[J]. CANCER CELL,2022,40(1):70-+.
APA Dong, Liangqing.,Lu, Dayun.,Chen, Ran.,Lin, Youpei.,Zhu, Hongwen.,...&Fan, Jia.(2022).p Proteogenomic characterization identifies clinically relevant subgroups of intrahepatic cholangiocarcinoma.CANCER CELL,40(1),70-+.
MLA Dong, Liangqing,et al."p Proteogenomic characterization identifies clinically relevant subgroups of intrahepatic cholangiocarcinoma".CANCER CELL 40.1(2022):70-+.

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来源：上海药物研究所

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