title: Telomerase reverse transcriptase methylation predicts lymph node metastasis and prognosis in patients with gastric cancer.
abstract: OBJECTIVE
  Telomerase activity is associated with cellular immortalization and is present in most human tumors but absent in normal tissues. The activity of telomerase reverse transcriptase (TERT), a catalytic telomerase subunit, correlates with telomerase activity in tumors. The objective of this study was to investigate TERT promoter methylation and its prognostic impact in gastric cancer (GC).
  
  
  METHODS
  The analysis of TERT promoter methylation was performed in tumors and corresponding normal tissues of 116 patients with GC using a highly sensitive Sequenom Epityper assay. The expression of TERT in GC tissues was measured by quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  The levels of TERT promoter methylation in GC samples were significantly higher than in normal adjacent tissues (P=0.002). Hypermethylation of TERT promoter was associated with high T-stage (P=0.024), late N-stage (P=0.006), and lymphovascular/neural invasion (P=0.035), without correlation with age, sex, or histological grade. Simple linear regression analysis showed that TERT mRNA correlated positively with TERT methylation (R (2)=0.562, P=0.001). Also, higher TERT mRNA expression was related to hypermethylation of TERT promoter in GC samples (P=0.005). Univariate analysis demonstrated that N-stage (P=0.002) and TERT promoter methylation (P=0.004) were predictive of overall survival. Furthermore, multivariate analysis confirmed that N-stage (P=0.013) and TERT promoter methylation (P=0.031) were independent prognostic indicators for overall survival.
  
  
  CONCLUSIONS
  Our data suggested that hypermethylation of TERT promoter may contribute to gastric wall invasion, lymph node metastasis, lymphovascular/neural invasion, and poor prognosis in GC. GC patients with hypermethylation of TERT promoter could be eligible for close follow-up.
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Guichao
authors.initials: G
authors.lastname: Li
authors.affiliation: Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: He
authors.affiliation: Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Fengping
authors.initials: F
authors.lastname: Yang
authors.affiliation: Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Guang
authors.initials: G
authors.lastname: He
authors.affiliation: Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Shen
authors.affiliation: Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Daizhan
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
keywords: gastric cancer; lymph node metastasis; methylation; prognosis; telomerase reverse transcriptase
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