Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University Taipei, Taiwan.
Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University Taipei, Taiwan ; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University Taipei, Taiwan.
Am J Transl Res. 2015 Jan 15;7(1):139-52. eCollection 2015.
Ovarian cancer is a cancer of high mortality. Aberrant gene methylation of tumor suppressor genes has been shown to be related to the development of malignancy. This study aimed to investigate the methylation of various genes in ovarian clear cell adenocarcinoma (OCCA) and ovarian endometrioid adenocarcinoma (OEA) and evaluate methylation biomarkers in terms of patient chemo-response and outcome. Eight candidate genes from 66 OCCA and 51 OEA patients were evaluated by methylation-specific polymerase chain reaction and capillary electrophoresis. Clinico-pathological parameters and patient outcomes were analyzed. The frequencies of gene methylation in RASSF1A (79% vs. 59%, p=0.025), E-cadherin (30% vs. 10%, p=0.011), and DLEC1 (71% vs. 43%, p=0.003) were higher in the patients with OCCA than in those with OEA. The chemo-resistant group had a significantly higher percentage of E-cadherin methylation (36.7% vs. 16.1%, p=0.036) than the chemo-sensitive group. In multivariate analysis (log-rank test), advanced stage (4.79 [2.10-10.94], p<0.001) was the only risk factor for mortality. Those with methylation of more than two out of three genes (E-cadherin, DLEC1, and SFRP5) had a shorter disease-free survival (1.89 [1.07-3.32], p=0.028) and overall survival (3.29 [1.57-6.87], p=0.002) than those with methylation of one or no gene. In advanced-stage malignancies, those with more than two out of the three gene methylations also had a shorter overall survival (3.86 [1.63-9.09], p=0.002) than those with methylation of only one or no gene. Patients with OCCA have different patterns of gene methylation than those with OEA. Methylation of the E-cadherin, DLEC1 and SFRP5 genes can be a prognostic biomarker for OCCA and OEA.
卵巢癌是一种死亡率较高的癌症。肿瘤抑制基因的异常甲基化与恶性肿瘤的发展有关。本研究旨在探讨卵巢透明细胞腺癌（OCCA）和卵巢子宫内膜样腺癌（OEA）中各种基因的甲基化情况，并评估甲基化标志物在患者化疗反应和预后方面的应用价值。通过甲基化特异性聚合酶链反应和毛细管电泳对 66 例 OCCA 和 51 例 OEA 患者的 8 个候选基因进行评估。分析临床病理参数和患者结局。RASSF1A（79%比 59%，p=0.025）、E-钙黏蛋白（30%比 10%，p=0.011）和 DLEC1（71%比 43%，p=0.003）基因在 OCCA 患者中的甲基化频率高于 OEA 患者。化疗耐药组的 E-钙黏蛋白甲基化比例明显高于化疗敏感组（36.7%比 16.1%，p=0.036）。多因素分析（log-rank 检验）显示，晚期（4.79 [2.10-10.94]，p<0.001）是死亡的唯一危险因素。3 个基因（E-钙黏蛋白、DLEC1 和 SFRP5）中超过 2 个基因发生甲基化的患者无疾病生存率（1.89 [1.07-3.32]，p=0.028）和总生存率（3.29 [1.57-6.87]，p=0.002）均较 1 个或无基因发生甲基化的患者更短。在晚期肿瘤中，3 个基因中超过 2 个基因发生甲基化的患者总生存率也较仅 1 个或无基因发生甲基化的患者更短（3.86 [1.63-9.09]，p=0.002）。与 OEA 相比，OCCA 患者的基因甲基化模式不同。E-钙黏蛋白、DLEC1 和 SFRP5 基因的甲基化可能是 OCCA 和 OEA 的预后生物标志物。
