Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials

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,...

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Autores: Montal, Robert, Andreu Oller, Carmen, Bassaganyas, Laia, Esteban Fabró, Roger, Moran, Sebastian, Montironi, Carla, Moeini, Agrin, Pinyol, Roser, Peix, Judit, Cabellos, Laia, Villanueva, Augusto, Sia, Daniela, Mazzaferro, Vincenzo, Esteller, Manel, Llovet i Bayer, Josep Maria
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/147217
Acceso en línea:https://hdl.handle.net/2445/147217
Access Level:acceso abierto
Palabra clave:Càncer de fetge
Oncogènesi
Liver cancer
Carcinogenesis
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spelling Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trialsMontal, RobertAndreu Oller, CarmenBassaganyas, LaiaEsteban Fabró, RogerMoran, SebastianMontironi, CarlaMoeini, AgrinPinyol, RoserPeix, JuditCabellos, LaiaVillanueva, AugustoSia, DanielaMazzaferro, VincenzoEsteller, ManelLlovet i Bayer, Josep MariaCàncer de fetgeOncogènesiLiver cancerCarcinogenesisThe 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.Nature Publishing Group2020202020192020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion3 p.application/pdfhttps://hdl.handle.net/2445/147217Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1038/s41416-019-0513-7British Journal of Cancer, 2019, vol. 121, p. 340–343https://doi.org/10.1038/s41416-019-0513-7info:eu-repo/grantAgreement/EC/H2020/667273(c) Montal et al., 2019info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1472172026-05-29T05:05:01Z
dc.title.none.fl_str_mv Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials
title Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials
spellingShingle Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials
Montal, Robert
Càncer de fetge
Oncogènesi
Liver cancer
Carcinogenesis
title_short Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials
title_full Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials
title_fullStr Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials
title_full_unstemmed Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials
title_sort Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials
dc.creator.none.fl_str_mv Montal, Robert
Andreu Oller, Carmen
Bassaganyas, Laia
Esteban Fabró, Roger
Moran, Sebastian
Montironi, Carla
Moeini, Agrin
Pinyol, Roser
Peix, Judit
Cabellos, Laia
Villanueva, Augusto
Sia, Daniela
Mazzaferro, Vincenzo
Esteller, Manel
Llovet i Bayer, Josep Maria
author Montal, Robert
author_facet Montal, Robert
Andreu Oller, Carmen
Bassaganyas, Laia
Esteban Fabró, Roger
Moran, Sebastian
Montironi, Carla
Moeini, Agrin
Pinyol, Roser
Peix, Judit
Cabellos, Laia
Villanueva, Augusto
Sia, Daniela
Mazzaferro, Vincenzo
Esteller, Manel
Llovet i Bayer, Josep Maria
author_role author
author2 Andreu Oller, Carmen
Bassaganyas, Laia
Esteban Fabró, Roger
Moran, Sebastian
Montironi, Carla
Moeini, Agrin
Pinyol, Roser
Peix, Judit
Cabellos, Laia
Villanueva, Augusto
Sia, Daniela
Mazzaferro, Vincenzo
Esteller, Manel
Llovet i Bayer, Josep Maria
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer de fetge
Oncogènesi
Liver cancer
Carcinogenesis
topic Càncer de fetge
Oncogènesi
Liver cancer
Carcinogenesis
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/147217
url https://hdl.handle.net/2445/147217
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41416-019-0513-7
British Journal of Cancer, 2019, vol. 121, p. 340–343
https://doi.org/10.1038/s41416-019-0513-7
info:eu-repo/grantAgreement/EC/H2020/667273
dc.rights.none.fl_str_mv (c) Montal et al., 2019
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Montal et al., 2019
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 3 p.
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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