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

Robert Montal, Carmen Andreu-Oller, Laia Bassaganyas, Roger Esteban-Fabró, Sebastián Moran, Carla Montironi, Agrin Moeini, Roser Pinyol, Judit Peix, Laia Cabellos, Augusto Villanueva, Daniela Sia, Vincenzo Mazzaferro, Manel Esteller, Josep M. Llovet

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)340-343
Number of pages4
JournalBritish Journal of Cancer
Volume121
Issue number4
DOIs
Publication statusPublished - Aug 13 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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