| Literature DB >> 34971568 |
Liangqing Dong1, Dayun Lu2, Ran Chen3, Youpei Lin1, Hongwen Zhu4, Zhou Zhang5, Shangli Cai5, Peng Cui5, Guohe Song1, Dongning Rao1, Xinpei Yi6, Yingcheng Wu1, Nixue Song2, Fen Liu3, Yunhao Zou3, Shu Zhang1, Xiaoming Zhang7, Xiaoying Wang1, Shuangjian Qiu1, Jian Zhou8, Shisheng Wang9, Xu Zhang10, Yongyong Shi11, Daniel Figeys10, Li Ding12, Pei Wang13, Bing Zhang6, Henry Rodriguez14, Qiang Gao15, Daming Gao16, Hu Zhou17, Jia Fan18.
Abstract
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.Entities:
Keywords: FGFR2 fusion; intrahepatic cholangiocarcinoma; molecular subgroups; oncogenic drivers; prognostic biomarkers; proteogenomics
Mesh：
Year: 2021 PMID： 34971568 DOI： 10.1016/j.ccell.2021.12.006
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743