title: Pyrosequencing quantified methylation level of BRCA1 promoter as prognostic factor for survival in breast cancer patient.
abstract: BRCA1 promoter methylation is an essential epigenetic transcriptional silencing mechanism, related to breast cancer (BC) occurrence and progression. We quantified the methylation level of BRCA1 promoter and evaluated its significance as prognostic and predictive factor. BRCA1 promoter methylation level was quantified by pyrosequencing in surgical cancerous and adjacent normal specimens from 154 BC patients. A follow up of 98 months was conducted to assess the correlation between BRCA1-methylation level vs. overall survival (OS) and disease free survival (DFS). The mean methylation level in BC tissues was significantly higher (mean 32.6%; median 31.9%) than in adjacent normal samples (mean 16.2%; median 13.0%) (P < 0.0001). Tumor stage (R = 0.6165, P < 0.0001) and size (R = 0.7328, P < 0.0001) were significantly correlated with the methylation level. Patients with unmethylated BRCA1 had a better OS and DFS compared to the methylated group (each P < 0.0001). BRCA1 promoter methylation level has a statistically significance on survival in BC patients (HazR = 1.465, P = 0.000) and is an independent prognostic factor for OS in BC patients (HazR = 2.042, P = 0.000). Patients with ductal type, HER2 negative, lymph node negative stage 1+2 tumors had a better OS and DFS. Classification of grades and molecular subtypes did not show any prognostic significance. Pyrosequencing is a precise and efficient method to quantify BRCA1 promoter methylation level, with a high potential for future clinical implication, as it identifies subgroups of patients with poorer prognosis.
authors.affiliation: Department of Breast Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, PR China.
authors.forename: Feng-Feng
authors.initials: FF
authors.lastname: Cai
authors.affiliation: Department of Molecular and Cellular Biology, School of Forensic Sciences, Xi'an Jiao Tong University Health Science Center, Xi'an, Shaanxi, PR China.
authors.forename: Su
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of General Practice, Yangpu Hospital, Tongji University School of Medicine, Shanghai, PR China.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, PR China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Lin
authors.affiliation: Department of Breast Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, PR China.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, PR China.
authors.forename: Jia-Xin
authors.initials: JX
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Qidong Hospital, Jiangsu, PR China.
authors.forename: Lian-Xin
authors.initials: LX
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Qidong Hospital, Jiangsu, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Thyroid and Breast Surgery, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, Zhejiang, PR China.
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Ding
authors.affiliation: Central Laboratory, Yangpu Hospital, Tongji University School of Medicine, Shanghai, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Shao
authors.affiliation: Department of Oncology, University Hospital of Basel, Basel, Switzerland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Biskup
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016019:Survival Analysis
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human
keywords: BRCA1; breast cancer; methylation; prognosis; pyrosequencing