Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/147217
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 Oncogènesi Liver cancer Carcinogenesis |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41416-019-0513-7 |
It is part of: | British Journal of Cancer, 2019, vol. 121, p. 340–343 |
URI: | http://hdl.handle.net/2445/147217 |
Related resource: | https://doi.org/10.1038/s41416-019-0513-7 |
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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