BRCA1 promoter hypermethylation in sporadic epithelial ovarian carcinoma: Association with low expression of BRCA1, improved survival and co‑expression of DNA methyltransferases

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; We,Minjie

doi:10.3892/ol.2014.1878

BRCA1 promoter hypermethylation in sporadic epithelial ovarian carcinoma: Association with low expression of BRCA1, improved survival and co‑expression of DNA methyltransferases

Authors:
- Xuefeng Bai
- Yingzi Fu
- Hui Xue
- Kejun Guo
- Zhiguo Song
- Zhaojin Yu
- Tianhong Jia
- Yuanyuan Yan
- Lin Zhao
- Xiaoyi Mi
- Enhua Wang
- Zhihong Zheng
- Haishan Zhao
- Weifan Yao
- Minjie We
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Affiliations: 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, Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: February 13, 2014 https://doi.org/10.3892/ol.2014.1878
Pages: 1088-1096

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Abstract

The breast cancer susceptibility gene 1 (BRCA1) inactivation in sporadic epithelial ovarian carcinoma (EOC) is common and low BRCA1 expression is associated with promoter hypermethylation. The clinical validation of BRCA1 methylation as a prognostic marker in EOC remains unresolved. The aim of the present study was to determine the aberrant promoter methylation of BRCA1 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 BRCA1 promoter hypermethylation was determined. The rate of BRCA1 methylation was observed to be 35.2% (50/142) in the EOCs; however, no methylation (0/32) was observed in the benign tumors. BRCA1 methylation was significantly associated with the downregulation of BRCA1 expression (P<0.001) and the frequency of BRCA1 methylation was greater in the carcinomas of patients whose tumor was bilateral than that of patients with a unilateral carcinoma (P=0.015). BRCA1 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 BRCA1. Thus, the present study provided support for BRCA1 promoter hypermethylation as a prognostic marker for survival in sporadic EOC, and co‑expression of DNMTs was observed to contribute to BRCA1 promoter hypermethylation.

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