title: CDH1 promoter methylation correlates with decreased gene expression and poor prognosis in patients with breast cancer.
abstract: The E-cadherin gene (CDH1) is associated with poor prognosis and metastasis in patients with breast cancer, and methylation of its promoter is correlated with decreased gene expression. However, there is currently no direct evidence that CDH1 promoter methylation indicates poor prognosis in patients with breast cancer. In the present study, methylation-specific polymerase chain reaction (PCR) was applied to detect the methylation status of the CDH1 promoter in 137 primary breast cancer, 85 matched normal breast tissue and 13 lung metastasis specimens. Reverse transcription-quantitative PCR was used to assess the relative expression levels of CDH1 mRNA, and correlation analysis between CDH1 methylation status, and gene expression, clinicopathological characteristics and patient survival was performed. Methylation of CDH1 was identified in 40.9% (56/137) of primary breast cancer specimens, 61.5% (8/13) of lung metastasis specimens and none of the matched normal breast specimens. The downregulation of CDH1 mRNA and E-cadherin protein expression were identified to be significantly correlated with CDH1 methylation (P<0.05). In addition, CDH1 methylation was significantly associated with lymph node metastasis and estrogen receptor status of patients (P<0.05). In univariate analyses, patients with CDH1 methylation exhibited poor overall survival (OS) and disease-free survival (DFS; P<0.05). Furthermore, multivariate analyses revealed that CDH1 methylation was an independent prognostic factor predicting poor OS (HR, 1.737; 95% CI, 0.957-3.766; P=0.041) and DFS (HR, 2.018; 95% CI, 2.057-3.845; P=0.033) in patients with breast cancer. Therefore, the present study suggests that CDH1 promoter methylation may be correlated with breast carcinogenesis and indicates poor prognosis in patients with breast cancer.
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Sida
authors.initials: S
authors.lastname: Qin
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Huangzhen
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: DU
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Respiration, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yamei
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Department of Hematology, Zoucheng People's Hospital, Zoucheng, Shandong 273500, P.R. China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Chongwen
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
keywords: E-cadherin gene; breast cancer; lymph node metastasis; methylation; prognosis