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Author:

Cai, Feng-Feng (Cai, Feng-Feng.) | Chen, Su (Chen, Su.) | Wang, Ming-Hong (Wang, Ming-Hong.) | Lin, Xiao-Yan (Lin, Xiao-Yan.) | Zhang, Lian (Zhang, Lian.) | Zhang, Jia-Xin (Zhang, Jia-Xin.) | Wang, Lian-Xin (Wang, Lian-Xin.) | Yang, Jun (Yang, Jun.) | Ding, Jin-Hua (Ding, Jin-Hua.) | Pan, Xin (Pan, Xin.) | Shao, Zhi-Ming (Shao, Zhi-Ming.) | Biskup, Ewelina (Biskup, Ewelina.)

Indexed by:

SCIE PubMed Scopus

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.

Keyword:

BRCA1 breast cancer methylation prognosis pyrosequencing

Author Community:

  • [ 1 ] [Cai, Feng-Feng; Lin, Xiao-Yan; Zhang, Lian] Tongji Univ, Sch Med, Yangpu Hosp, Dept Breast Surg, Shanghai 200092, Peoples R China
  • [ 2 ] [Chen, Su] Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Forens Sci, Dept Mol & Cellular Biol, Xian 710049, Shaanxi, Peoples R China
  • [ 3 ] [Wang, Ming-Hong] Tongji Univ, Sch Med, Yangpu Hosp, Dept Gen Practice, Shanghai 200092, Peoples R China
  • [ 4 ] [Zhang, Jia-Xin] Fudan Univ, Shanghai Canc Ctr, Dept Breast Surg, Shanghai 200433, Peoples R China
  • [ 5 ] [Wang, Lian-Xin; Yang, Jun] Qidong Hosp, Dept Gen Surg, Qidong, Jiangsu, Peoples R China
  • [ 6 ] [Ding, Jin-Hua] Lihuili Eastern Hosp, Dept Thyroid & Breast Surg, Ningbo Med Ctr, Ningbo, Zhejiang, Peoples R China
  • [ 7 ] [Pan, Xin] Tongji Univ, Yangpu Hosp, Sch Med, Cent Lab, Shanghai 200092, Peoples R China
  • [ 8 ] [Shao, Zhi-Ming] Fudan Univ, Dept Oncol, Shanghai Med Coll, Dept Breast Surg,Key Lab Breast Canc Shanghai,Sha, Shanghai 200433, Peoples R China
  • [ 9 ] [Biskup, Ewelina] Univ Basel Hosp, Dept Oncol, CH-4031 Basel, Switzerland
  • [ 10 ] [Cai, Feng-Feng]Tongji Univ, Sch Med, Yangpu Hosp, Dept Breast Surg, Shanghai 200092, Peoples R China
  • [ 11 ] [Lin, Xiao-Yan]Tongji Univ, Sch Med, Yangpu Hosp, Dept Breast Surg, Shanghai 200092, Peoples R China
  • [ 12 ] [Zhang, Lian]Tongji Univ, Sch Med, Yangpu Hosp, Dept Breast Surg, Shanghai 200092, Peoples R China
  • [ 13 ] [Chen, Su]Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Forens Sci, Dept Mol & Cellular Biol, Xian 710049, Shaanxi, Peoples R China
  • [ 14 ] [Wang, Ming-Hong]Tongji Univ, Sch Med, Yangpu Hosp, Dept Gen Practice, Shanghai 200092, Peoples R China
  • [ 15 ] [Zhang, Jia-Xin]Fudan Univ, Shanghai Canc Ctr, Dept Breast Surg, Shanghai 200433, Peoples R China
  • [ 16 ] [Wang, Lian-Xin]Qidong Hosp, Dept Gen Surg, Qidong, Jiangsu, Peoples R China
  • [ 17 ] [Yang, Jun]Qidong Hosp, Dept Gen Surg, Qidong, Jiangsu, Peoples R China
  • [ 18 ] [Ding, Jin-Hua]Lihuili Eastern Hosp, Dept Thyroid & Breast Surg, Ningbo Med Ctr, Ningbo, Zhejiang, Peoples R China
  • [ 19 ] [Pan, Xin]Tongji Univ, Yangpu Hosp, Sch Med, Cent Lab, Shanghai 200092, Peoples R China
  • [ 20 ] [Shao, Zhi-Ming]Fudan Univ, Dept Oncol, Shanghai Med Coll, Dept Breast Surg,Key Lab Breast Canc Shanghai,Sha, Shanghai 200433, Peoples R China
  • [ 21 ] [Biskup, Ewelina]Univ Basel Hosp, Dept Oncol, CH-4031 Basel, Switzerland

Reprint Author's Address:

  • Tongji Univ, Sch Med, Yangpu Hosp, Dept Breast Surg, Shanghai 200092, Peoples R China.; Pan, X (reprint author), Tongji Univ, Yangpu Hosp, Sch Med, Cent Lab, Shanghai 200092, Peoples R China.; Shao, ZM (reprint author), Fudan Univ, Dept Oncol, Shanghai Med Coll, Dept Breast Surg,Key Lab Breast Canc Shanghai,Sha, Shanghai 200433, Peoples R China.

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Source :

ONCOTARGET

ISSN: 1949-2553

Year: 2016

Issue: 19

Volume: 7

Page: 27499-27510

5 . 1 6 8

JCR@2016

5 . 1 6 8

JCR@2016

ESI Discipline: MOLECULAR BIOLOGY & GENETICS;

ESI HC Threshold:280

JCR Journal Grade:2

Cited Count:

WoS CC Cited Count: 9

SCOPUS Cited Count: 14

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 11

Affiliated Colleges:

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