Table of Contents
ISRN Pathology
Volume 2011, Article ID 273924, 10 pages
Review Article

Chronic Hypoxia Emerging as One of the Driving Forces behind Gene Expression and Prognosis of Hepatocellular Carcinoma

Liver Research Facility and Lab of Hepatology, University Hospital Gasthuisberg-Leuven, Herestraat 49, bus 703, 3000 Leuven, Belgium

Received 24 March 2011; Accepted 12 April 2011

Academic Editors: A. B. Galosi, C. K. Panda, A. Wincewicz, and T. Yazawa

Copyright © 2011 Jos F. van Pelt et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors and an important cause of death. It has become evident that the tumor microenvironment, including hypoxia, plays a major role in the development of HCC. This paper focuses on the role of chronic hypoxia in HCC. Recently, we have shown the importance of chronic hypoxia on gene expression and behavior of liver cells. Using a cell culture model, we identified a distinct gene expression pattern and demonstrated clinical relevance for a 7-gene subset that can predict survival and early recurrence in patients. Recently, it was also shown that chronic hypoxia is associated with the upregulation of β-catenin and Hif1α and that suppression of β-catenin reduced the metastatic potential of the tumor. Both studies demonstrate the importance of chronic hypoxia for the prognosis of HCC. Identifying the molecular pathways can help us to understand the mechanisms responsible for tumor aggressiveness.