Shimogai R, Kigawa J, Itamochi H, Iba T, Kanamori Y, Oishi T, Shimada M, Sato S, Kawaguchi W, Sato S, Terakawa N
Department of Obstetrics and Gynecology, Tottori University, School of Medicine, Nishimachi, Yonago, Japan.
Int J Gynecol Cancer. 2008 May-Jun;18(3):499-505. doi: 10.1111/j.1525-1438.2007.01055.x.
We conducted study to determine whether and how the expression of the hypoxia-inducible factor 1alpha (HIF-1alpha) gene relates to outcome in patients with epithelial ovarian cancer. A total of 66 patients with epithelial ovarian cancer, who underwent primary surgery followed by platinum-based chemotherapy, were entered into this study. We confirmed the expression of HIF-1alpha and the vascular endothelial growth factor (VEGF) by immunohistochemistry. To determine the quantity of HIF-1alpha and VEGF expression, messenger RNA of each gene was measured by real-time reverse transcription-polymerase chain reaction. The cutoff values were determined by the receiver-operating characteristic curve according to survival. The protein expressions of HIF-1alpha and VEGF were strongly observed in the cancer cells. The cutoff value of HIF-1alpha and VEGF gene expression was 6.0 and 3.0, respectively. The expression of HIF-1alpha did not relate to clinical stage, but tumor with low VEGF expression was observed more frequently in stage I patients. The response rate to chemotherapy did not differ between high and low expression of both genes. The overall survival for patients with high expression of HIF-1alpha was significantly lower, but disease-free survival did not differ between high and low expression of HIF-1alpha, whereas both overall and disease-free survival for patients with high expression of VEGF were significantly lower. Multivariate analysis revealed that FIGO stage and HIF-1alpha expression were independent prognostic factors but that VEGF was not. The present study suggested that the expression level of HIF-1alpha could be an independent prognostic factor in epithelial ovarian cancer.
我们开展了一项研究，以确定缺氧诱导因子1α（HIF-1α）基因的表达是否以及如何与上皮性卵巢癌患者的预后相关。共有66例接受了初次手术并随后接受铂类化疗的上皮性卵巢癌患者纳入本研究。我们通过免疫组织化学法证实了HIF-1α和血管内皮生长因子（VEGF）的表达。为了确定HIF-1α和VEGF表达的量，通过实时逆转录-聚合酶链反应测量每个基因的信使核糖核酸。根据生存情况通过受试者工作特征曲线确定临界值。在癌细胞中强烈观察到HIF-1α和VEGF的蛋白表达。HIF-1α和VEGF基因表达的临界值分别为6.0和3.0。HIF-1α的表达与临床分期无关，但在I期患者中更频繁地观察到低VEGF表达的肿瘤。两个基因高表达和低表达患者对化疗的反应率没有差异。HIF-1α高表达患者的总生存期显著较低，但HIF-1α高表达和低表达患者的无病生存期没有差异，而VEGF高表达患者的总生存期和无病生存期均显著较低。多因素分析显示，国际妇产科联盟（FIGO）分期和HIF-1α表达是独立的预后因素，但VEGF不是。本研究表明，HIF-1α的表达水平可能是上皮性卵巢癌的一个独立预后因素。
