title: Association of promoter methylation of RUNX3 gene with the development of esophageal cancer: a meta analysis.
abstract: BACKGROUND
  Runt-related transcription factor 3 (RUNX3) is a member of the runt-domain family of transcription factors. Emerging evidence indicates that RUNX3 is a tumor suppressor gene in several types of human cancers including esophageal cancer. However, the association between RUNX3 promoter methylation and esophageal cancer remains unclear. Here we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of RUNX3 promoter methylation on the incidence of esophageal cancer.
  
  
  METHODS
  A detailed literature search was made on Medline, Pubmed and Web of Science for related research publications written in English and/or Chinese. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data were performed, the odds ratios (OR) were calculated and summarized respectively.
  
  
  RESULTS
  Final analysis of 558 patients from 9 eligible studies was performed. The result showed that RUNX3 methylation was significantly higher in esophageal cancer than in normal squamous mucosa from the proximal resection margin or esophageal benign lesions (OR = 2.85, CI = 2.01-4.05, P<0.00001). The prevalence of lymph node involvement, tumor size (T1-T2 vs T3-T4) and histological grade was significantly greater in RUNX3-negative cases (RUNX3 unmethylated groups) than in RUNX3-positive cases (OR = 0.25, CI = 0.14-0.43, P<0.00001). RUNX3 methylation was significantly higher in esophageal adenocarcinoma (EAC) than Barrett's esophagus (OR = 0.35, CI = 0.20-0.59, P<0.0001). In addition, the pooled HR for overall survival (OS) showed that decreased RUNX3 expression was associated with worse survival in esophageal cancer (HR = 4.31, 95% CI = 2.57-7.37, P<0.00001).
  
  
  CONCLUSIONS
  The results of this meta-analysis suggest that RUNX3 methylation is associated with an increased risk, progression as well as worse survival in esophageal cancer. RUNX3 methylation, which induces the inactivation of RUNX3 gene, plays an important role in esophageal carcinogenesis.
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P. R. China.
authors.forename: Xiuguang
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P. R. China.
authors.forename: Jieqing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P. R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Qi
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P. R. China.
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Gastroscopy, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P. R. China.
authors.forename: Wenju
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P. R. China.
authors.forename: Fulei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P. R. China.
authors.forename: Hanchen
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P. R. China.
authors.forename: Baosheng
authors.initials: B
authors.lastname: Zhao
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics*; D019175:DNA Methylation; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D006801:Humans; D011379:Prognosis; D011401:Promoter Regions, Genetic; D017594:Publication Bias
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit