Proteogenomic characterization of non-functional clinically relevant subgroups
文献类型：期刊论文
| 作者 | Ji, Shunrong5; Cao, Lihua4; Gao, Jing3; Du, Yang4; Ye, Zeng5; Lou, Xin5; Liu, Fen2; Zhang, Yehan1; Xu, Junfeng5,22; Shi, Xiaohan20 |
| 刊名 | CANCER CELL
 |
| 出版日期 | 2025-04-14 |
| 卷号 | 43期号:4页码:36 |
| ISSN号 | 1535-6108 |
| DOI | 10.1016/j.ccell.2025.03.016 |
| 英文摘要 | The majority of neuroendocrine neoplasms in pancreas are non-functional pancreatic neuroendocrine tumors (NF-PanNETs), which exhibit a high occurrence of distant metastases with limited therapeutic options. Here, we perform a comprehensive molecular characterization of 108 NF-PanNETs through integrative analysis of genomic, transcriptomic, proteomic, and phosphoproteomic profiles. Proteogenomic analysis provides functional insights into the genomic driver alterations of NF-PanNETs, revealing a potential mediator of MEN1 alterations using Men1-conditional knockout mice. Machine-learning-based modeling uncovers a three-protein signature as an independent prognostic factor, which is validated by an independent external cohort. Proteomic and phosphoproteomic-based stratification identifies four subtypes with distinct molecular characteristics, immune microenvironments, and clinicopathological features. Drug screening using patient-derived tumor organoids identifies cyclin-dependent kinase (CDK) 5 and Calcium Voltage-Gated Channel Subunit Alpha1 D (CACNA1D) as ubiquitous and subtype-specific targets, respectively, with in vivo validation using xenograft models. Together, our proteogenomic analyses illustrate a comprehensive molecular landscape of NF-PanNETs, revealing biological insights and therapeutic vulnerabilities. |
| WOS关键词 | PANCREATIC NEUROENDOCRINE TUMORS ; SOMATIC MUTATIONS ; DOUBLE-BLIND ; CANCER ; NETWORK ; PROTEIN ; GROWTH ; MTOR ; CDK5 ; IDENTIFICATION |
| 资助项目 | National Key Research and Development Program of China[2020YFA0803203] ; National Natural Science Foundation of China[22425703] ; National Natural Science Foundation of China[82141129] ; National Natural Science Foundation of China[81925029] ; National Natural Science Foundation of China[W2412036] ; National Natural Science Foundation of China[82273253] ; National Natural Science Foundation of China[82303943] ; National Natural Science Foundation of China[82230098] ; National Natural Science Foundation of China[32221002] ; National Natural Science Foundation of China[U21A20374] ; National Natural Science Foundation of China[32100525] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB0830000] ; Shanghai Leading Talent Program of Eastern Talent Plan[LJ2023123] ; Sailing Project of Science and Technology Commission of Shanghai Municipality[23YF1406900] ; China Postdoc-toral Science Foundation[2023M730670] ; Shanghai Municipal Science and Technology Major Project[21JC1401500] ; Scientific Innovation Project of Shanghai Education Committee[2019 01 07 00 07 E00057] ; Baidu Foundation of China[2019BD012] ; CAS project for young scientists in basic research[SHDC2020CR1006A] ; Clinical Research Plan of Shanghai Hospital Development Center ; Xuhui District Artificial Intelligence Medical Hospital Cooperation Project[XKFZ2415] ; Xuhui District Artificial Intelligence Medical Hospital Cooperation Project[ZY202408] ; Science Foundation of Peking University Cancer Hospital ; [2019YFA0802102] ; [82141104] ; [YSBR-014] ; [2021-011] |
| WOS研究方向 | Oncology ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001473209300001 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317536]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Gao, Daming; Jin, Gang; Zhou, Hu; Wu, Jianmin; Yu, Xianjun |
| 作者单位 | 1.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Key Lab Multicell Syst, Shanghai Key Lab Mol Androl,Shanghai Inst Biochem, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Key Lab Multicell Syst, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Peking Univ, Ctr Canc Bioinformat, State Key Lab Holist Integrat Management Gastroint, Beijing Key Lab Carcinogenesis & Translat Res,Canc, Beijing 100142, Peoples R China 5.Fudan Univ, Shanghai Canc Ctr, Dept Pancreat Surg, Shanghai 200032, Peoples R China 6.Peking Univ, Int Canc Inst, Beijing 100191, Peoples R China 7.Shanghai Inst Mat Med Univ Ottawa Joint Res Ctr Sy, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 8.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci, Key Lab Syst Hlth Sci Zhejiang Prov, Hangzhou 310024, Peoples R China 9.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 10.Johns Hopkins Univ, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD 21231 USA |
| 推荐引用方式 GB/T 7714 | Ji, Shunrong,Cao, Lihua,Gao, Jing,et al. Proteogenomic characterization of non-functional clinically relevant subgroups[J]. CANCER CELL,2025,43(4):36. |
| APA | Ji, Shunrong.,Cao, Lihua.,Gao, Jing.,Du, Yang.,Ye, Zeng.,...&Yu, Xianjun.(2025).Proteogenomic characterization of non-functional clinically relevant subgroups.CANCER CELL,43(4),36. |
| MLA | Ji, Shunrong,et al."Proteogenomic characterization of non-functional clinically relevant subgroups".CANCER CELL 43.4(2025):36. |
入库方式： OAI收割
来源：上海药物研究所
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