Proteogenomic characterization identifies clinically relevant subgroups of intrahepatic cholangiocarcinoma

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 wit...

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Vydané v:Cancer cell Ročník 40; číslo 1; s. 70
Hlavní autori: Dong, Liangqing, Lu, Dayun, Chen, Ran, Lin, Youpei, Zhu, Hongwen, Zhang, Zhou, Cai, Shangli, Cui, Peng, Song, Guohe, Rao, Dongning, Yi, Xinpei, Wu, Yingcheng, Song, Nixue, Liu, Fen, Zou, Yunhao, Zhang, Shu, Zhang, Xiaoming, Wang, Xiaoying, Qiu, Shuangjian, Zhou, Jian, Wang, Shisheng, Zhang, Xu, Shi, Yongyong, Figeys, Daniel, Ding, Li, Wang, Pei, Zhang, Bing, Rodriguez, Henry, Gao, Qiang, Gao, Daming, Zhou, Hu, Fan, Jia
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 10.01.2022
Predmet:
Bile Duct Neoplasms - genetics
Bile Duct Neoplasms - pathology
Bile Ducts, Intrahepatic - pathology
Cholangiocarcinoma - genetics
Cholangiocarcinoma - pathology
Humans
Liver - pathology
Mutation - genetics
Prognosis
Proteogenomics - methods
Proteomics
Tumor Microenvironment - immunology
prognostic biomarkers
molecular subgroups
oncogenic drivers
proteogenomics
intrahepatic cholangiocarcinoma
FGFR2 fusion
ISSN:1878-3686, 1878-3686
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Shrnutí: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.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1878-3686
1878-3686
DOI:10.1016/j.ccell.2021.12.006