Abstract
Background: Hepatoblastoma (HB) is a rare embryonal liver tumor
occurring in the pediatric population, and although intrinsic biological
differences between tumors can impact HBs prognosis, few groups have
studied this aspect. Given the crescent relevance of epigenetic
mechanisms in the genesis and progression of these tumors, we aim to
classify HB samples according to the different stages of liver
development as well as DNA methylation machinery. Procedures: Using
bioinformatics tools, we evaluate the expression of 24 genes associated
with epigenetics and stages of hepatocyte differentiation as well as
global DNA methylation to propose a stratification model for HB.
Results: Based on the gene expression profiles of DNA methylation
machinery and hepatocyte differentiation markers, HBs were clustered
into three groups. Besides reinforcing the molecular heterogeneity of
these embryonal tumors, our data propose that a panel of 13 genes can be
used for HB stratification (TET1, TET2, TET3, DNMT1, DNMT3A, UHRF1, ALB,
CYP3A4, TDO2, UGT1A1, AFP, HNF4A, and FOXA2). DNA methylation machinery
exerts a key role in the characterization of HBs, directly reflected in
diverse DNA methylation content. Moreover, we suggest that the group of
HBs presenting similarity with differentiated livers, such as
upregulation of mature hepatocyte markers, decreased expression of DNA
methylation enzymes and higher global methylation levels are associated
with a worse prognosis. Conclusions: HBs are heterogeneous tumors and
our findings point out the role of the epigenetic machinery in the
samples characterization, suggesting the need of new stratification
system for patients with HBs.