Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/90179
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Type: | Journal article |
Title: | IGFBP7 is associated with poor prognosis in oesophageal adenocarcinoma and is regulated by promoter DNA methylation |
Author: | Smith, E. Ruszkiewicz, A. Jamieson, G. Drew, P. |
Citation: | British Journal of Cancer, 2014; 110(3):775-782 |
Publisher: | Nature Publishing Group |
Issue Date: | 2014 |
ISSN: | 0007-0920 1532-1827 |
Statement of Responsibility: | E Smith, A R Ruszkiewicz, G G Jamieson, and P A Drew |
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. CONCLUSION: 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. |
Keywords: | Humans Adenocarcinoma Esophageal Neoplasms Insulin-Like Growth Factor Binding Proteins Biopsy Gene Expression Regulation, Neoplastic Aged Aged, 80 and over Cell Line, Tumor Middle Aged Promoter Regions, Genetic DNA Methylation Kaplan-Meier Estimate Prognosis Female Male |
Rights: | © 2014 Cancer Research UK. All rights reserved |
DOI: | 10.1038/bjc.2013.783 |
Published version: | http://dx.doi.org/10.1038/bjc.2013.783 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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hdl_90179.pdf | Published version | 1.41 MB | Adobe PDF | View/Open |
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