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Molecular Cancer
Published in: Molecular Cancer 1/2012

Open Access 01-12-2012 | Research

Genetic signatures shared in embryonic liver development and liver cancer define prognostically relevant subgroups in HCC

Authors: Diana Becker, Ioannis Sfakianakis, Markus Krupp, Frank Staib, Aslihan Gerhold-Ay, Anja Victor, Harald Binder, Maria Blettner, Thorsten Maass, Snorri Thorgeirsson, Peter R Galle, Andreas Teufel

Published in: Molecular Cancer | Issue 1/2012

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Abstract

Multiple activations of individual genes during embryonic liver and HCC development have repeatedly prompted speculations about conserved embryonic signatures driving cancer development. Recently, the emerging discussion on cancer stem cells and the appreciation that generally tumors may develop from progenitor cells of diverse stages of cellular differentiation has shed increasing light on the overlapping genetic signatures between embryonic liver development and HCC. However there is still a lack of systematic studies investigating this area. We therefore performed a comprehensive analysis of differentially regulated genetic signaling pathways in embryonic and liver cancer development and investigated their biological relevance.
Genetic signaling pathways were investigated on several publically available genome wide microarray experiments on liver development and HCC. Differentially expressed genes were investigated for pathway enrichment or underrepresentation compared to KEGG annotated pathways by Fisher exact evaluation. The comparative analysis of enrichment and under representation of differentially regulated genes in liver development and HCC demonstrated a significant overlap between multiple pathways. Most strikingly we demonstrated a significant overlap not only in pathways expected to be relevant to both conditions such as cell cycle or apoptosis but also metabolic pathways associated with carbohydrate and lipid metabolism. Furthermore, we demonstrated the clinical significance of these findings as unsupervised clustering of HCC patients on the basis of these metabolic pathways displayed significant differences in survival.
These results indicate that liver development and liver cancer share similar alterations in multiple genetic signaling pathways. Several pathways with markedly similar patterns of enrichment or underrepresentation of various regulated genes between liver development and HCC are of prognostic relevance in HCC. In particular, the metabolic pathways were identified as novel prognostically relevant players in HCC development.
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Metadata
Title
Genetic signatures shared in embryonic liver development and liver cancer define prognostically relevant subgroups in HCC
Authors
Diana Becker
Ioannis Sfakianakis
Markus Krupp
Frank Staib
Aslihan Gerhold-Ay
Anja Victor
Harald Binder
Maria Blettner
Thorsten Maass
Snorri Thorgeirsson
Peter R Galle
Andreas Teufel
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2012
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-11-55

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