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Proteogenomic characterization of cholangiocarcinoma.
Deng, Mengjie; Ran, Peng; Chen, Lingli; Wang, Yunzhi; Yu, Zixiang; Cai, Ke; Feng, Jinwen; Qin, Zhaoyu; Yin, Yanan; Tan, Subei; Liu, Yang; Xu, Chen; Shi, Guoming; Ji, Yuan; Zhao, Jian-Yuan; Zhou, Jian; Fan, Jia; Hou, Yingyong; Ding, Chen.
Afiliación
  • Deng M; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development , School of Life Sciences , Institute of Biomedical Sciences , Human Phenome Institute , Zhongshan Hospital , Fudan University , Shanghai , China.
  • Ran P; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development , School of Life Sciences , Institute of Biomedical Sciences , Human Phenome Institute , Zhongshan Hospital , Fudan University , Shanghai , China.
  • Chen L; Department of Pathology , Zhongshan Hospital , Fudan University , Shanghai , China.
  • Wang Y; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development , School of Life Sciences , Institute of Biomedical Sciences , Human Phenome Institute , Zhongshan Hospital , Fudan University , Shanghai , China.
  • Yu Z; Department of Pathology , Zhongshan Hospital , Fudan University , Shanghai , China.
  • Cai K; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development , School of Life Sciences , Institute of Biomedical Sciences , Human Phenome Institute , Zhongshan Hospital , Fudan University , Shanghai , China.
  • Feng J; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development , School of Life Sciences , Institute of Biomedical Sciences , Human Phenome Institute , Zhongshan Hospital , Fudan University , Shanghai , China.
  • Qin Z; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development , School of Life Sciences , Institute of Biomedical Sciences , Human Phenome Institute , Zhongshan Hospital , Fudan University , Shanghai , China.
  • Yin Y; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development , School of Life Sciences , Institute of Biomedical Sciences , Human Phenome Institute , Zhongshan Hospital , Fudan University , Shanghai , China.
  • Tan S; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development , School of Life Sciences , Institute of Biomedical Sciences , Human Phenome Institute , Zhongshan Hospital , Fudan University , Shanghai , China.
  • Liu Y; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development , School of Life Sciences , Institute of Biomedical Sciences , Human Phenome Institute , Zhongshan Hospital , Fudan University , Shanghai , China.
  • Xu C; Department of Pathology , Zhongshan Hospital , Fudan University , Shanghai , China.
  • Shi G; Department of Liver Surgery and Transplantation , Liver Cancer Institute , Zhongshan Hospital , Fudan University , Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education , Shanghai , China.
  • Ji Y; Department of Pathology , Zhongshan Hospital , Fudan University , Shanghai , China.
  • Zhao JY; Institute for Development and Regenerative Cardiovascular Medicine , MOE-Shanghai Key Laboratory of Children's Environmental Health , Xinhua Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
  • Zhou J; Department of Liver Surgery and Transplantation , Liver Cancer Institute , Zhongshan Hospital , Fudan University , Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education , Shanghai , China.
  • Fan J; Key Laboratory of Medical Epigenetics and Metabolism , Institutes of Biomedical Sciences , Fudan University , Shanghai , China.
  • Hou Y; Department of Liver Surgery and Transplantation , Liver Cancer Institute , Zhongshan Hospital , Fudan University , Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education , Shanghai , China.
  • Ding C; Key Laboratory of Medical Epigenetics and Metabolism , Institutes of Biomedical Sciences , Fudan University , Shanghai , China.
Hepatology ; 77(2): 411-429, 2023 02 01.
Article en En | MEDLINE | ID: mdl-35716043
ABSTRACT
BACKGROUND AND

AIMS:

Cholangiocarcinoma (CCA) is a highly heterogeneous cancer with limited understanding and few effective therapeutic approaches. We aimed at providing a proteogenomic CCA characterization to inform biological processes and treatment vulnerabilities. APPROACH AND

RESULTS:

Integrative genomic analysis with functional validation uncovered biological perturbations downstream of driver events including DPCR1 , RBM47 mutations, SH3BGRL2 copy number alterations, and FGFR2 fusions in CCA. Proteomic clustering identified three subtypes with distinct clinical outcomes, molecular features, and potential therapeutics. Phosphoproteomics characterized targetable kinases in CCA, suggesting strategies for effective treatment with CDK and MAPK inhibitors. Patients with CCA with HBV infection showed increased antigen processing and presentation (APC) and T cell infiltration, conferring a favorable prognosis compared with those without HBV infection. The characterization of extrahepatic CCA recommended the feasible application of vascular endothelial-derived growth factor inhibitors. Multiomics profiling presented distinctive molecular characteristics of the large bile duct and the small bile duct of intrahepatic CCA. The immune landscape further revealed diverse tumor immune microenvironments, suggesting immune subtypes C1 and C5 might benefit from immune checkpoint therapy. TCN1 was identified as a potential CCA prognostic biomarker, promoting cell growth by enhancing vitamin B12 metabolism.

CONCLUSIONS:

We characterized the proteogenomic landscape of 217 CCAs with 197 paired normal adjacent tissues and identified their subtypes and potential therapeutic targets. The multiomics analyses with other databases and some functional validations have indicated strategies regarding the clinical, biological, and therapeutic approaches to the management of CCA.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de los Conductos Biliares / Colangiocarcinoma / Proteogenómica Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Hepatology Año: 2023 Tipo del documento: Article País de afiliación: China
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de los Conductos Biliares / Colangiocarcinoma / Proteogenómica Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Hepatology Año: 2023 Tipo del documento: Article País de afiliación: China