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Title: Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials
Author: 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
Keywords: Càncer de fetge
Liver cancer
Issue Date: 9-Jul-2019
Publisher: Nature Publishing Group
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.
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It is part of: British Journal of Cancer, 2019, vol. 121, p. 340–343
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Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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