Department of General-, Visceral- and Transplantation Surgery, University Hospital Essen, Essen, Germany.
Langenbecks Arch Surg. 2010 Apr;395(4):395-405. doi: 10.1007/s00423-009-0590-9. Epub 2010 Feb 18.
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.
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.
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.
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.
本研究旨在阐明低氧诱导因子 1A（HIF1A）在肝细胞癌（HCC）及其相应非恶性肝组织中的表达作用，并将其与接受根治性肝切除术后 HCC 患者的临床结局相关联。
我们采用定量 RT-PCR 法检测了 53 例接受 HCC 根治性肝切除术治疗的患者 HCC 及其相应非恶性肝组织中的 HIF1A 表达情况。我们对非恶性肝组织中 HIF1A 高表达和低表达的患者亚组进行了高密度基因表达分析和通路分析。
非恶性肝组织中 HIF1A 的高表达是肿瘤复发和生存的预测指标。与 HIF1A 高表达患者相比，非恶性肝组织中 HIF1A 低表达患者的估计 1 年和 5 年无病生存率明显更好（分别为 88.9%比 67.9%和 61.0%比 22.6%，p = 0.008）。基于利用高密度基因表达谱进行的分子通路分析，鉴定到了与 HIF1A 相关的分子网络，其中包含了参与细胞迁移、细胞归巢和细胞间相互作用的基因。
本研究确定了一个可能的潜在新机制，该机制有助于预测 HCC 的预后。非恶性肝组织中 HIF1A 的失调及其相关通路为潜在的调节环境提供了基础，该调节环境可能增强或允许 HCC 在根治性切除术后复发。
