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Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials
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Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials
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Journal Article
Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials
2019
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ alpha-Fetoproteins - analysis
/ alpha-Fetoproteins - genetics
/ Antibodies, Monoclonal, Humanized - therapeutic use
/ Biomedical and Life Sciences
/ Carcinoma, Hepatocellular - blood
/ Carcinoma, Hepatocellular - drug therapy
/ Carcinoma, Hepatocellular - genetics
/ Humans
/ Liver Neoplasms - drug therapy
/ Oncology
/ Tumors
