Pyrosequencing quantified methylation level of BRCA1 promoter as prognostic factor for survival in breast cancer patient
| Autor: | Ming Hong Wang, Xin Pan, Jin Hua Ding, Lian Xin Wang, Xiao Yan Lin, Su Chen, Ewelina Biskup, Jun Yang, Feng‑Feng Cai, Lian Zhang, Jia Xin Zhang, Zhi Ming Shao |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology Prognostic factor medicine.medical_specialty Pathology Breast Neoplasms Biology Disease-Free Survival 03 medical and health sciences breast cancer 0302 clinical medicine Breast cancer Internal medicine medicine Humans Epigenetics Stage (cooking) Promoter Regions Genetic skin and connective tissue diseases Survival analysis BRCA1 Protein Methylation DNA Methylation Middle Aged BRCA1 Prognosis medicine.disease Survival Analysis pyrosequencing 030104 developmental biology 030220 oncology & carcinogenesis DNA methylation Pyrosequencing Female methylation Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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