Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Shanghai, PR China.
BMC Cancer. 2009 Dec 1;9:418. doi: 10.1186/1471-2407-9-418.
Despite well-studied tumor hypoxia in laboratory, little is known about the association with other pathophysiological events in the clinical view. We investigated the prognostic value of hypoxia-inducible factor-1 alpha (HIF-1alpha) in hepatocellular carcinoma (HCC), and its correlations with inflammation, angiogenesis and MYC oncogene.
In a random series of 110 HCC patients, the mRNA of HIF-1alpha, inflammation related factors (COX-2, MMP7 and MMP9), angiogenesis related factors (VEGF and PDGFRA) and MYC in tumor tissue were detected by real-time RT-PCR and HIF-1alpha protein was assessed by immunohistochemistry. The correlations between HIF-1alpha mRNA and the factors mentioned previously, the relationship between HIF-1alpha and clinicopathologic features, and the prognostic value were analyzed.
The expression of both HIF-1alpha mRNA and protein in HCC were independent prognostic factors for overall survival (OS) (P = 0.012 and P = 0.021, respectively) and disease-free survival (DFS) (P = 0.004 and P = 0.007, respectively) as well. Besides, the high expression of HIF-1alpha mRNA and protein proposed an advanced BCLC stage and more incidence of vascular invasion. The mRNA of HIF-1alpha had significantly positive correlations to that of COX-2, PDGFRA, MMP7, MMP9, MYC, except VEGF. In addition to HIF-1alpha, COX-2 and PDGFRA were also independent prognosticators for OS (P = 0.004 and P = 0.010, respectively) and DFS (P = 0.010 and P = 0.038, respectively).
HIF-1alpha in HCC plays an important role in predicting patient outcome. It may influence HCC biological behaviors and affect the tumor inflammation, angiogenesis and act in concert with the oncogene MYC. Attaching importance to HIF-1alpha in HCC may improve the prognostic and therapeutic technique.
尽管实验室中对肿瘤缺氧进行了深入研究，但在临床角度上，对其与其他病理生理事件的关联知之甚少。我们研究了缺氧诱导因子-1 阿尔法（HIF-1alpha）在肝细胞癌（HCC）中的预后价值，及其与炎症、血管生成和 MYC 癌基因的相关性。
在随机选择的 110 例 HCC 患者中，通过实时 RT-PCR 检测肿瘤组织中 HIF-1alpha、炎症相关因子（COX-2、MMP7 和 MMP9）、血管生成相关因子（VEGF 和 PDGFRA）和 MYC 的 mRNA，并用免疫组织化学法检测 HIF-1alpha 蛋白。分析 HIF-1alpha mRNA 与上述因子的相关性、HIF-1alpha 与临床病理特征的关系及其预后价值。
HCC 中 HIF-1alpha mRNA 和蛋白的表达均是总生存（OS）（P = 0.012 和 P = 0.021）和无病生存（DFS）（P = 0.004 和 P = 0.007）的独立预后因素。此外，HIF-1alpha mRNA 和蛋白高表达提示 BCLC 分期较高，血管侵犯发生率较高。HIF-1alpha mRNA 与 COX-2、PDGFRA、MMP7、MMP9、MYC 的 mRNA 均呈显著正相关，除了 VEGF。除 HIF-1alpha 外，COX-2 和 PDGFRA 也是 OS（P = 0.004 和 P = 0.010）和 DFS（P = 0.010 和 P = 0.038）的独立预后因素。
HCC 中的 HIF-1alpha 在预测患者预后方面发挥着重要作用。它可能影响 HCC 的生物学行为，并与癌基因 MYC 共同作用。重视 HCC 中的 HIF-1alpha 可能会改善预后和治疗技术。
