期刊
BRITISH JOURNAL OF CANCER
卷 121, 期 4, 页码 340-343出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41416-019-0513-7
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资金
- FSEOM-Boehringer Ingelheim Grant
- la Caixa INPhINIT Fellowship Grant for Doctoral studies at Spanish Research Centres of Excellence
- la Caixa Banking Foundation [100010434, LCF/BQ/IN17/11620024, LCF/PR/PR15/11100003]
- Beatriu de Pinos grant from Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR, Generalitat de Catalunya)
- MICINN/MINECO [BES-2017-081286]
- Josep Font grant from Hospital Clinic de Barcelona
- European Commission/Horizon 2020 Program (HEPCAR) [667273-2]
- Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd)-ISCIII
- U.S. Department of Defense [CA150272P3]
- Tisch Cancer Institute (Cancer Center Grant) [P30-CA196521]
- Gilead Sciences Research Scholar Program in Liver Disease
- Associazione Italiana per la Ricerca sul Cancro
- Oncology Research Project of the Italian Ministry of Health
- Department of Health PERIS project [SLT/002/16/00374]
- AGAUR projects of the Catalan Government (Generalitat de Catalunya) [2017SGR1080, 2014SGR633, 2009SGR1315]
- Spanish Institute of Health Carlos III (ISCIII) [DTS16/00153]
- Integrated Project of Excellence [PIE13/00022]
- Ministerio de Economia y Competitividad (MINECO) grant [SAF2014-55000-R]
- European Development Regional Fund A way to achieve Europe (ERDF)
- CIBERONC [CIBER 2016 CB16/12/00312]
- Cellex Foundation
- National Cancer Institute [P30-CA196521]
- EIT Health (CRISH2) [18053]
- Accelerator Award (CRUCK) (HUNTER) [C9380/A26813]
- Accelerator Award (AECC) (HUNTER) [C9380/A26813]
- Accelerator Award (AIRC) (HUNTER) [C9380/A26813]
- Samuel Waxman Cancer Research Foundation
- Spanish National Health Institute [SAF2016-76390]
- Generalitat de Catalunya/AGAUR [SGR-1358]
The clinical utility of serum alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC) is widely recognised. However, a clear understanding of the mechanisms of AFP overexpression and the molecular traits of patients with AFP-high tumours are not known. We assessed transcriptome data, whole-exome sequencing data and DNA methylome profiling of 520 HCC patients from two independent cohorts to identify distinct molecular traits of patients with AFP-high tumours (serum concentration > 400 ng/ml), which represents an accepted prognostic cut-off and a predictor of response to ramucirumab. Those AFP-high tumours (18% of resected cases) were characterised by significantly lower AFP promoter methylation (p < 0.001), significant enrichment of progenitor-cell features (CK19, EPCAM), higher incidence of BAP1 oncogene mutations (8.5% vs 1.6%) and lower mutational rates of CTNNB1 (14% vs 30%). Specifically, AFP-high tumours displayed significant activation of VEGF signalling (p <0.001), which might provide the rationale for the reported benefit of ramucirumab in this subgroup of patients.
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