Hypoxia-inducible factor-1 alpha, in association with inflammation, angiogenesis and MYC, is a critical prognostic factor in patients with HCC after surgery.
Hypoxia-inducible factor-1 alpha, in association with inflammation, angiogenesis and MYC, is a critical prognostic factor in patients with HCC after surgery.
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缺氧诱导因子 1 α 与炎症、血管生成和 MYC 相关，是 HCC 患者术后的关键预后因素。
DOI：
10.1186/1471-2407-9-418
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发表时间：
2009-12-01
期刊：
影响因子：
3.8
通讯作者：
Fan J
中科院分区：
文献类型：
--
作者：
Dai CX;Gao Q;Qiu SJ;Ju MJ;Cai MY;Xu YF;Zhou J;Zhang BH;Fan J
尽管在实验室中对肿瘤缺氧进行了充分研究，但从临床角度来看，其与其他病理生理事件的关联却知之甚少。我们研究了缺氧诱导因子 1 α (HIF-1α) 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。随机选取 110 例 HCC 患者，采用实时 RT-PCR 检测肿瘤组织中 HIF-1α、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，并采用免疫组化法检测肿瘤组织中 HIF-1α 蛋白。分析HIF-1α mRNA与前述因素的相关性、HIF-1α与临床病理特征的关系以及预后价值。 HCC 中 HIF-1α mRNA 和蛋白的表达也是总生存期 (OS)（分别为 P = 0.012 和 P = 0.021）和无病生存期 (DFS)（分别为 P = 0.004 和 P = 0.007）的独立预后因素。此外，HIF-1α mRNA和蛋白的高表达提示BCLC分期较晚，血管侵犯的发生率较高。除VEGF外，HIF-1α的mRNA与COX-2、PDGFRA、MMP7、MMP9、MYC的mRNA均呈显着正相关。除了 HIF-1α 之外，COX-2 和 PDGFRA 也是 OS（分别为 P = 0.004 和 P = 0.010）和 DFS（分别为 P = 0.010 和 P = 0.038）的独立预测因子。 HCC 中的 HIF-1α 在预测患者预后方面发挥着重要作用。它可能影响HCC生物学行为，影响肿瘤炎症、血管生成并与癌基因MYC协同作用。在 HCC 中重视 HIF-1α 可能会改善预后和治疗技术。
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.