中国肿瘤生物治疗杂志2013，Vol.20Issue(3)：317-322,6.DOI:10.3872/j.issn.1007-385X.2013.03.011
GADD45A基因在人贲门腺癌组织中的异常甲基化和表达及其临床意义
Expression and aberrant methylation of growth arrest and DNA-damageinducible 45 alpha gene in human gastric cardia adenocarcinoma tissues and its clinical significance
摘要
Abstract
Objective:To investigate the expression and aberrant methylation of growth arrest and DNA-damageinducible 45 alpha (GADD45A) gene in gastric cardia adenocarcinoma (GCA) and to explore its clinical significance.Methods:Tissue samples in GCA patients (138 cases) were selected from Fourth Hospital of Hebei University during 2004 to 2007.Bisulfite sequencing (BS-Seq),bisulfite conversion-methylation specific polymerase chain reaction (BS-MSP),reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry methods were used respectively to detect the methylation status,mRNA and protein expression of GADD45A gene in GCA tissues and the para-carcinoma normal tissues.Results:The methylation frequency of four CpG sites in distal promoter of GADD45A in GCA tissues (44.93％,[62/138]) was significantly higher than that in the para-carcinoma normal tissues (0.00％,0/138) (P ＜0.01).The methylation frequency of 4 CpG sites in stage Ⅲ and Ⅳ GCA tissues was significantly higher than that in stage Ⅰ and Ⅱ GCA tissues (P ＜ 0.05).However,the methylation status GADD45A in GCA tissues was not correltaed with age,gender and pathological differentiation (P ＞ 0.05).For GADD45A region 2 and 3 located in proximal promoter and exon 1,no methylation was detected in GCA and the para-carcinoma normal tissues.The expression of GADD45A mRNA and positive expression rate of GADD45A protein in GCA tissues were significantly lower than those in the para-carcinoma normal tissues ([0.35 ± 0.15] vs [0.78 ± 0.26],42.75 ％ vs 71.01％,P ＜ 0.05) and was associated with methylation status of 4 CpG sites in distal promoter (r =-0.52,P ＜ 0.01).Conclusion:Hypermethylation of four CpG sites in distal promoter of GADD45A gene may be responsible for the decreased expression of GADD45A in GCA.关键词
贲门腺癌/生长阻滞和DNA损伤诱导45A基因/甲基化Key words
gastric cardia adenocarcinoma (GCA)/GADD45A gene/ methylation分类
医药卫生引用本文复制引用
张清泉,董稚明,郭炜,张明慧,崔蕾..GADD45A基因在人贲门腺癌组织中的异常甲基化和表达及其临床意义[J].中国肿瘤生物治疗杂志,2013,20(3):317-322,6.基金项目
国家自然科学基金资助项目(No.81101854) （No.81101854）
河北省科技厅资助项目(No.072761223).Project supported by the National Natural Science Foundation of China(No.81101854).and the Science and Technology y Bureau of Hebei Province(No.072761223) （No.072761223）
