IGFBP7 与食管腺癌的不良预后相关，且受启动子 DNA 甲基化调控。
IGFBP7 is associated with poor prognosis in oesophageal adenocarcinoma and is regulated by promoter DNA methylation.
机构信息
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.
SA Pathology, Frome Road, Adelaide 5000, South Australia, Australia.
出版信息
Br J Cancer. 2014 Feb 4;110(3):775-82. doi: 10.1038/bjc.2013.783. Epub 2013 Dec 19.
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.
背景
我们研究了 IGFBP7 沉默是否与食管腺癌患者的生存有关。
方法
使用组织微阵列中 65 例未经新辅助治疗的食管腺癌患者肿瘤的免疫组织化学法来确定 IGFBP7 的蛋白表达。通过融化曲线分析在细胞系和患者组织中确定 IGFBP7 启动子的 DNA 甲基化。
结果
在 65 例患者中的 34 例（52%）食管腺癌中观察到 IGFBP7 的表达，与中位（11 对 92 个月）和 5 年生存率（25%对 52%）显著降低相关。多变量分析将表达确定为生存的独立预后指标（危险比=3.24，95%置信区间=1.58-6.67，P 值=0.0014）。IGFBP7 的高甲基化与细胞系和患者组织中基因表达的沉默相关（P 值=0.0225）。在 15 例 Barrett 食管患者中的 2 例（13%）和 17 例食管腺癌患者中的 3 例（18%）中观察到鳞状粘膜中的甲基化。在 18 例 Barrett 黏膜活检中的 14 例（78%）和 34 例食管腺癌患者中的 23 例（68%）中观察到甲基化。
结论
在食管腺癌患者中，IGFBP7 蛋白表达降低与生存时间延长相关。IGFBP7 启动子的甲基化与基因表达沉默相关，在 Barrett 食管和食管腺癌中很常见。
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