Deregulation von HIF1-alpha und Hypoxie regulierten Signalwegen in HCC und nicht-malignen Lebergewebe – Einfluss des Host-Stromas auf die Prognose des HCC

Purpose: The aim of this study was to elucidate the role of hypoxia-inducible factor 1 alpha 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 geneexpression 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.