Detection of aberrant methylation of a six-gene panel in serum DNA for diagnosis of breast cancer
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Ming Shan1,2,*, Huizi Yin1,*, Junnan Li3, Xiaobo Li4, Dong Wang5, Yonghui Su1, Ming Niu1, Zhenbin Zhong1, Ji Wang1, Xianyu Zhang1, Wenli Kang6, Da Pang1,2
1Department of Breast Cancer Surgery, the Affiliated Tumor Hospital of Harbin Medical University, Harbin, P.R. China
2Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, P.R. China
3Department of Epidemiology and Biostatistics, Harbin Medical University, Harbin, P.R. China
4Department of Pathology, Harbin Medical University, Harbin, P.R. China
5College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P.R. China
6Department of Oncology, General Hospital of Heilongjiang Province Land Reclamation Headquarters, Harbin, P.R. China
*These authors have contributed equally to this work
Da Pang, e-mail: firstname.lastname@example.org
Keywords: breast cancer, DNA methylation, diagnosis, MethyLight
Received: December 08, 2015 Accepted: February 11, 2016 Published: February 23, 2016
Detection of breast cancer at an early stage is the key for successful treatment and improvement of outcome. However the limitations of mammography are well recognized, especially for those women with premenopausal breast cancer. Novel approaches to breast cancer screening are necessary, especially in the developing world where mammography is not feasible. In this study, we examined the promoter methylation of six genes (SFN, P16, hMLH1, HOXD13, PCDHGB7 and RASSF1a) in circulating free DNA (cfDNA) extracted from serum. We used a high-throughput DNA methylation assay (MethyLight) to examine serum from 749 cases including breast cancer patients, patients with benign breast diseases and healthy women. The six-gene methylation panel test achieved 79.6% and 82.4% sensitivity with a specificity of 72.4% and 78.1% in diagnosis of breast cancer when compared with healthy and benign disease controls, respectively. Moreover, the methylation panel positive group showed significant differences in the following independent variables: (a) involvement of family history of tumors; (b) a low proliferative index, ki-67; (c) high ratios in luminal subtypes. Additionally the panel also complemented some breast cancer cases which were neglected by mammography or ultrasound. These data suggest that epigenetic markers in serum have potential for diagnosis of breast cancer.
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