Integrative proteogenomic analysis provides molecular insights and clinical significance in gallbladder cancer
文献类型：期刊论文
| 作者 | Fu, Zile9; Song, Yuanli9,10; Liu, Fen11,12; Chen, Lv9; Cai, Shangli13; Cui, Peng13; Wang, Guoqiang13; Xie, Wenchuan13; Zhang, Shu9; Ding, Li14 |
| 刊名 | CANCER CELL
 |
| 出版日期 | 2026-02-09 |
| 卷号 | 44期号:2页码:33 |
| ISSN号 | 1535-6108 |
| DOI | 10.1016/j.ccell.2025.12.014 |
| 英文摘要 | Gallbladder cancer (GBC) is a highly aggressive malignancy with dismal outcomes. To dissect its molecular characteristics and identify potential therapeutic avenues, we performed proteogenomic characterization of 195 tumors and 135 adjacent non-cancerous gallbladder tissues. Integrative analyses highlighted TP53 and ELF3 mutations as key drivers disrupting signaling and metabolism. ErbB2 amplification, a pivotal genomic event, was associated with reduced canonical PI3K/AKT and RAS/MAPK/ERK signaling yet enhanced proliferative activity. We discovered potential gain-of-function mutations in ErbB2 and ErbB3 predicted to enhance ErbB2-ErbB3 heterodimer activity. ACAT1 and PHGDH were identified as metabolic drivers of GBC liver invasion. Integrated molecular and immune subtyping delineated four distinct multi-omics and immune microenvironment subtypes, each carrying prognostic and therapeutic relevance. Although rare, neuroendocrine GBC was separately characterized, revealing MEIS1 as a potential regulator of neuroendocrine-like features. Together, this study establishes a proteogenomic landscape of GBC, providing biological insights and guiding future translational efforts. |
| WOS关键词 | MUTATIONS ; RESISTANCE ; CARCINOMA ; RESOURCE ; PACKAGE ; ERBB3 ; CHEMOTHERAPY ; DEPENDENCY ; INHIBITOR ; DISCOVERY |
| 资助项目 | National Key Research and Development Program of China[2023YFF1205101] ; National Key Research and Development Program of China[2020YFA0803203] ; National Natural Science Foundation of China[U23A6010] ; National Natural Science Foundation of China[22425703] ; National Natural Science Foundation of China[81925029] ; National Natural Science Foundation of China[82230098] ; National Natural Science Foundation of China[32221002] ; National Natural Science Foundation of China[82121002] ; Science and Technology Commission of Shanghai Municipality[23JS1410200] ; Science and Technology Commission of Shanghai Municipality[24ZR1480600] ; Shanghai Leading Talent Program of Eastern Talent Plan[LJ2023123] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB0830000] ; Chinese Academy of Sciences[083GJHZ2025038MI] ; CAS project for young scientists in basic research[YSBR-014] ; Basic Medical Research Foundation of the Naval Medical University[2021MS15] ; Shanghai Municipal Science and Technology Major Projects ; Chinese Academy of Sciences ; Zhongshan Hospital ; Shanghai Institute of Materia Medica ; Fudan University ; US National Cancer Institute's Office of Cancer Clinical Proteomics Research (Clinical Proteomic Tumor Analysis Consortium [CPTAC]) |
| WOS研究方向 | Oncology ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001689328200001 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322990]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Gaog, Wei; Gao, Qiang; Gao, Daming; Zhou, Hu; Fan, Jia |
| 作者单位 | 1.NCI, Div Canc Treatment & Diag, Off Canc Clin Prote Res, NIH, Bethesda, MD 20892 USA 2.Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Xian 710061, Peoples R China 3.Xi An Jiao Tong Univ, Affiliated Hosp 1, Inst Adv Surg Technol & Engn, Xian 710061, Peoples R China 4.Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Gen Surg, Sch Med, Shanghai 200092, Peoples R China 5.Fudan Univ, Human Phenome Inst, State Key Lab Genet Engn, Shanghai 200433, Peoples R China 6.Beijing Inst Life, Beijing Proteome Res Ctr, Natl Ctr Prot Sci Beijing, State Key Lab Med Prote, Beijing 102206, Peoples R China 7.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, 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.Fudan Univ, Zhongshan Hosp,Minist Educ, Liver Canc Inst,Key Lab Carcinogenesis & Canc Inva, Dept Hepatobiliary Surg & Transplantat, Shanghai 200032, Peoples R China 10.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Fu, Zile,Song, Yuanli,Liu, Fen,et al. Integrative proteogenomic analysis provides molecular insights and clinical significance in gallbladder cancer[J]. CANCER CELL,2026,44(2):33. |
| APA | Fu, Zile.,Song, Yuanli.,Liu, Fen.,Chen, Lv.,Cai, Shangli.,...&Fan, Jia.(2026).Integrative proteogenomic analysis provides molecular insights and clinical significance in gallbladder cancer.CANCER CELL,44(2),33. |
| MLA | Fu, Zile,et al."Integrative proteogenomic analysis provides molecular insights and clinical significance in gallbladder cancer".CANCER CELL 44.2(2026):33. |
入库方式： OAI收割
来源：上海药物研究所
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