title: IGFBP7 is associated with poor prognosis in oesophageal adenocarcinoma and is regulated by promoter DNA methylation.
abstract: BACKGROUND
  We examined whether silencing of IGFBP7 was associated with survival in patients with oesophageal adenocarcinoma.
  
  
  METHODS
  Protein expression of IGFBP7 was determined using immunohistochemistry in a tissue microarray representing tumours from 65 patients with oesophageal adenocarcinoma who had not had neoadjuvant therapy. DNA methylation of the IGFBP7 promoter was determined with the melt curve analysis in cell lines and patient tissues.
  
  
  RESULTS
  Expression of IGFBP7 was observed in the oesophageal adenocarcinoma of 34 out of 65 (52%) patients and was associated with significantly reduced median (11 vs 92 months) and 5-year survival (25% vs 52%). Multivariate analysis identified expression as an independent prognostic indicator for survival (hazard ratio=3.24, 95% confidence interval=1.58-6.67, P-value=0.0014). Hypermethylation of IGFBP7 was associated with silencing of gene expression in cell lines and patient tissues (P-value=0.0225). Methylation was observed in the squamous mucosa of 2 out of 15 (13%) patients with Barrett's oesophagus and 3 out of 17 (18%) with oesophageal adenocarcinoma. Methylation was observed in 14 out of 18 (78%) of biopsies of Barrett's mucosa and 23 out of 34 (68%) patients with oesophageal adenocarcinoma.
  
  
  CONCLUSIONS
  Reduced IGFBP7 protein expression was associated with longer survival in patients with oesophageal adenocarcinoma. Methylation of the IGFBP7 promoter was associated with silencing of gene expression and was frequent in Barrett's oesophagus and oesophageal adenocarcinoma.
authors.affiliation: Solid Cancer Regulation Research Group, Discipline of Surgery, Basil Hetzel Institute for Translational Health Research, The University of Adelaide, The Queen Elizabeth Hospital, 28 Woodville Road, Woodville South 5011, South Australia, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Smith
authors.affiliation: SA Pathology, Frome Road, Adelaide 5000, South Australia, Australia.
authors.forename: A R
authors.initials: AR
authors.lastname: Ruszkiewicz
authors.affiliation: Discipline of Surgery, The University of Adelaide, Adelaide 5005, South Australia, Australia.
authors.forename: G G
authors.initials: GG
authors.lastname: Jamieson
authors.affiliation: 1] Solid Cancer Regulation Research Group, Discipline of Surgery, Basil Hetzel Institute for Translational Health Research, The University of Adelaide, The Queen Elizabeth Hospital, 28 Woodville Road, Woodville South 5011, South Australia, Australia [2] School of Nursing and Midwifery, Flinders University, Bedford Park 5042, South Australia, Australia.
authors.forename: P A
authors.initials: PA
authors.lastname: Drew
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1