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

Molecular Cancer

Research

Markus Krupp¹  Peter R Galle¹  Frank Staib¹  Diana Becker¹  Ioannis Sfakianakis¹  Thorsten Maass¹  Andreas Teufel²  Aslihan Gerhold-Ay³  Maria Blettner³  Harald Binder³  Anja Victor³  Snorri Thorgeirsson⁴ 

[1] Department of Medicine I, Johannes Gutenberg University, Mainz, Germany;Department of Medicine I, Johannes Gutenberg University, Mainz, Germany;Department of Medicine I, Johannes Gutenberg University, Building 605, Langenbeckstr. 1, 55101, Mainz, Germany;Institute of Medical Biostatistics, Epidemiology and Informatics(IMBEI), Johannes Gutenberg University, Mainz, Germany;Laboratory of Experimental Carcinogenesis (LEC), National Cancer Institute, National Institutes of Health, Bethesda, MD, USA;

关键词: Unsupervised Cluster;    Liver Development;    Cancer Stem Cell Hypothesis;    Bile Acid Biosynthesis;    Pathway Category;   

DOI  :  10.1186/1476-4598-11-55

 received in 2012-03-27, accepted in 2012-07-12,  发布年份 2012

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Becker et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.