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| Home > Articles > Published articles > Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma : |
(Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Institut d'Investigació Biomèdica de Bellvitge) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Icahn School of Medicine at Mount Sinai) (Icahn School of Medicine at Mount Sinai) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institució Catalana de Recerca i Estudis Avançats)| Date: | 2019 |
| Abstract: | 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. |
| Grants: | Ministerio de Ciencia e Innovación MINECO/BES-2017-081286 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009SGR1315 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014SGR633 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR1080 Instituto de Salud Carlos III PIE13-00022 Instituto de Salud Carlos III DTS16-00153 Ministerio de Economía y Competitividad SAF2014-55000-R European Commission 667273 Instituto de Salud Carlos III SAF2016-76390 Agència de Gestió d'Ajuts Universitaris i de Recerca SGR-1358 |
| Note: | Altres ajuts: Robert Montal is supported by a FSEOM-Boehringer Ingelheim Grant. Carmen Andreu-Oller has received financial support through the "la Caixa" INPhINIT Fellowship Grant for Doctoral studies at Spanish Research Centres of Excellence, from "la Caixa" Banking Foundation (ID 100010434), fellowship code (LCF/BQ/IN17/ 11620024). Carla Montironi is a recipient of Josep Font grant from Hospital Clinic de Barcelona. Augusto Villanueva is supported by U.S. Department of Defense (CA150272P3) and Tisch Cancer Institute (Cancer Center Grant P30-CA196521). Manel Esteller is supported by CIBER 2016 CB16/12/00312 (CIBERONC); the Cellex Foundation; "la Caixa" Banking Foundation (LCF/PR/PR15/11100003). Josep M. Llovet is supported by National Cancer Institute (P30-CA196521). ; Generalitat de Catalunya, Departament de Salut, Projecte PERIS SLT-002-16-00374 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Cancer genomics ; Hepatocellular carcinoma |
| Published in: | British Journal of Cancer, Vol. 121 Núm. 4 (13 2019) , p. 340-343, ISSN 1532-1827 |
