中国肿瘤生物治疗杂志2017，Vol.24Issue(7)：708-715,8.DOI:10.3872/j.issn.1007-385x.2017.07.003
DACT1基因不同区域异常甲基化对食管鳞癌患者预后的影响
Effect of aberrant methylation of DACT1 gene different regions on prognosis of the patients with esophageal squamous cell cancer
摘要
Abstract
Objective:To investigate the methylation status of dishevelled-binding antagonist of beta-catenin 1 (DACT1) gene in CpG islands shore and transcription start site(TSS) regions in esophageal squamous cell cancer (ESCC) cell lines and ESCC samples,and to explore the possible effect on gene transcription and the prognosis of ESCC patients.Methods:MSP and RT-PCR methods were applied respectively to examine the methylation of DACT1 gene in two regions and its mRNA expression in ESCC cell lines (TE 1,TE 13,T.Tn,Eca109) andESCC samples which from the high risk area of upper digestive tract cancer in Hebei Province.Results:The negative or weak expression of DACT1 mRNA was detected in four ESCC cell lines.After treated with 5-aza-2'-deoxycytidine (5-azadC,a demethylation agent),the expression level of DACT1 mRNA was obviously increased.Meanwhile,The result of MSP showed that the methylation bands were obviously weakened or disappeared.The level of DACT1 mRNA expression had no obviously change after treated with trichostatin A (TSA).Decreased mRNA expression of DACT1 was observed in ESCC tumor tissues comparing with non-cancerous tissues(P＜0.01),and associated with the methylation status of TSS region(P＜0.01).The hypermethylation of DACT 1 in CpG islands shore region was observed both in tumor and corresponding adjacent tissues but wasn't related to the transcriptional inhibition of DACT1.The result of survival analysis showed that the methylation status of DACT1 in TSS region was associated with ESCC patients' prognosis(P＜0.01).Conclusion:The highpermethylation of DACT1 in TSS region was one of the mechanisms causing genes silencing in ESCC and may serve as prognostic methylation biomarkers for ESCC patients.关键词
食管鳞状细胞癌/β-环连蛋白抑制基因1/甲基化Key words
esophageal squamous cell cancer (ESCC)/dishevelled-binding antagonist of beta-catenin 1 (DACT1)/methylation分类
医药卫生引用本文复制引用
郭艳丽,周珍,邝钢,郭炜,董稚明,沈素朋,梁佳,郭鑫..DACT1基因不同区域异常甲基化对食管鳞癌患者预后的影响[J].中国肿瘤生物治疗杂志,2017,24(7):708-715,8.基金项目
国家自然科学基金资助项目(No.81472335,No.81572441),河北省自然科学基金资助项目(No.H2013206315).Project supported by the National Nature Science Foundation of China(No.81472335,No.81572441),and the Natures Science Foundation of Hebei Province (No.H2013206315) （No.81472335,No.81572441）
