Bai Xuefeng, Fu Yingzi, Xue Hui, Guo Kejun, Song Zhiguo, Yu Zhaojin, Jia Tianhong, Yan Yuanyuan, Zhao Lin, Mi Xiaoyi, Wang Enhua, Zheng Zhihong, Zhao Haishan, Yao Weifan, Wei Minjie
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
Department of Obstetrics and Gynecology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
Oncol Lett. 2014 Apr;7(4):1088-1096. doi: 10.3892/ol.2014.1878. Epub 2014 Feb 13.
The breast cancer susceptibility gene 1 () inactivation in sporadic epithelial ovarian carcinoma (EOC) is common and low BRCA1 expression is associated with promoter hypermethylation. The clinical validation of methylation as a prognostic marker in EOC remains unresolved. The aim of the present study was to determine the aberrant promoter methylation of in benign and malignant ovarian tumor tissues, to establish the association with the clinicopathological significance and the prognostic value. Additionally, the contribution of DNA methyltransferase (DNMT) expression to promoter hypermethylation was determined. The rate of methylation was observed to be 35.2% (50/142) in the EOCs; however, no methylation (0/32) was observed in the benign tumors. methylation was significantly associated with the downregulation of expression (P<0.001) and the frequency of methylation was greater in the carcinomas of patients whose tumor was bilateral than that of patients with a unilateral carcinoma (P=0.015). methylation was significantly associated with the preoperative serum carbohydrate antigen-125 level (P=0.013), improved overall survival (P=0.005) and disease-free survival (P=0.007). In addition, a significant correlation was observed between the co-expression of DNMTs and the methylation status of . Thus, the present study provided support for promoter hypermethylation as a prognostic marker for survival in sporadic EOC, and co-expression of DNMTs was observed to contribute to promoter hypermethylation.
散发性上皮性卵巢癌（EOC）中乳腺癌易感基因1（）失活很常见，且BRCA1低表达与启动子高甲基化有关。EOC中甲基化作为预后标志物的临床验证仍未解决。本研究的目的是确定良性和恶性卵巢肿瘤组织中启动子的异常甲基化，建立其与临床病理意义及预后价值的关联。此外，还确定了DNA甲基转移酶（DNMT）表达对启动子高甲基化的作用。观察到EOC中甲基化率为35.2%（50/142）；然而，在良性肿瘤中未观察到甲基化（0/32）。甲基化与表达下调显著相关（P<0.001），肿瘤为双侧的患者癌组织中的甲基化频率高于单侧癌患者（P=0.015）。甲基化与术前血清糖类抗原125水平显著相关（P=0.013），与总生存期改善（P=0.005）和无病生存期改善（P=0.007）相关。此外，观察到DNMTs的共表达与的甲基化状态之间存在显著相关性。因此，本研究支持启动子高甲基化作为散发性EOC生存的预后标志物，并且观察到DNMTs的共表达促成了启动子高甲基化。
