, Volume 395, Issue 4, pp 395-405
Date: 18 Feb 2010

Deregulation of HIF1-alpha and hypoxia-regulated pathways in hepatocellular carcinoma and corresponding non-malignant liver tissue—influence of a modulated host stroma on the prognosis of HCC

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Abstract

Purpose

The aim of this study was to elucidate the role of HIF1A expression in hepatocellular carcinoma (HCC) and the corresponding non-malignant liver tissue and to correlate it with the clinical outcome of HCC patients after curative liver resection.

Methods

HIF1A expression was determined by quantitative RT-PCR in HCC and corresponding non-malignant liver tissue of 53 patients surgically treated for HCC. High-density gene expression analysis and pathway analysis was performed on a selected subset of patients with high and low HIF1A expression in the non-malignant liver tissue.

Results

HIF1A over-expression in the apparently non-malignant liver tissue was a predictor of tumor recurrence and survival. The estimated 1-year and 5-year disease-free survival was significantly better in patients with low HIF1A expression in the non-malignant liver tissue when compared to those patients with high HIF1 expression (88.9% vs. 67.9% and 61.0% vs. 22.6%, respectively, p = 0.008). Based on molecular pathway analysis utilizing high-density gene-expression profiling, HIF1A related molecular networks were identified that contained genes involved in cell migration, cell homing, and cell–cell interaction.

Conclusion

Our study identified a potential novel mechanism contributing to prognosis of HCC. The deregulation of HIF1A and its related pathways in the apparently non-malignant liver tissue provides for a modulated environment that potentially enhances or allows for HCC recurrence after curative resection.

Authors Contributions

Study concept and design: Frank Weber, Maximilian Bockhorn, Chritoph E. Broelsch, Andrea Frilling
Acquisition of data: Frank Simon, Maximilian Bockhorn, Frank Weber, Christian Praha, Hideo A. Baba, Christoph E. Broelsch, Andrea Frilling
Analysis and interpretation of data: Frank Weber, Frank Simon, Maximilian Bockhorn, Christian Praha
Drafting of manuscript: Frank Weber, Frank Simon, Maximilian Bockhorn
Critical revision of manuscript: Frank Weber, Frank Simon, Maximilian Bockhorn, Christian Praha, Hideo A. Baba, Christoph E. Broelsch, Andrea Frilling
Frank Simon and Maximilian Bockhorn contributed equally to this work.
“Best of Abstracts—Chirurgisches Forum 2010, Deutsche Gesellschaft für Chirurgie”