Gadd45G基因在食管鳞癌组织中的异常甲基化及表达  

Aberrant methylation and expression of growth arrest and DNA-damage-inducible 45G gene in esophageal squamous-cell carcinoma

作　　者：郭炜[1] 朱铁年[1] 董稚明[2] 张明慧[2] 崔蕾[2] 

机构地区：[1]白求恩国际和平医院肿瘤科,河北石家庄050082 [2]河北医科大学第四医院/河北省肿瘤研究所病理研究室,河北石家庄050011

出　　处：《肿瘤》2013年第1期74-80,共7页Tumor

基　　金：河北省医学科学研究重点课题计划(编号:20090465)

摘　　要：目的:检测食管鳞状细胞癌(esophageal squamous cell carcinoma,本文中简称为食管鳞癌)中生长阻滞和DNA损伤诱导基因G(growth arrest and DNA-damage-inducible 45gamma,Gadd45G)的异常甲基化及表达,并探讨其临床意义。方法:分别应用亚硫酸氢盐转换-甲基化特异性PCR(bisul te conversion-methylation specific PCR,BS-MSP)、RT-PCR及免疫组织化学法检测Gadd45G基因在食管鳞癌组织及癌旁正常组织中的甲基化、mRNA及蛋白表达情况,并分析Gadd45G异常甲基化及表达水平与食管鳞癌患者临床病理特征的相关性。结果:食管鳞癌组织中Gadd45G远端启动子区(region1)的甲基化率为4.7%(6/128),与癌旁正常组织(0.0%,0/128)相比差异有统计学意义(P<0.05);Gadd45G此区域发生甲基化的食管鳞癌组织其mRNA和蛋白表达水平与未发生甲基化的食管鳞癌组织相比差异无统计学意义(P>0.05)。食管鳞癌组织Gadd45G第2个CpG岛的近端启动子区(region2)及第1外显子区(region3)的甲基化率相同,均为45.3%(58/128),与癌旁正常组织相比(0.0%,0/128),差异具有统计学意义(P<0.01);且食管鳞癌组织中此2个区域的甲基化与TNM分期及组织学分化程度密切相关(P<0.05)。食管鳞癌组织中Gadd45G的mRNA和蛋白表达水平显著低于癌旁正常组织(P<0.05),并与TNM分期和组织学分化程度密切相关(P<0.05),与其近端启动子区(region2)及第1外显子区(region3)的甲基化状态之间也有明显相关性(P<0.05)。结论:Gadd45G基因近端启动子区及第1外显子区的高甲基化导致其表达降低,这可能是食管鳞癌发生的机制之一。Objective： To investigate the aberrant methylation and expression of Gadd45G （growth arrest and DNA-damage-inducible 45 gamma） gene in ESCC （esophageal squamous-cell carcinoma） tissues, and to elucidate its clinical significance. Methods： Bisulfite conversion-methylation specific PCR （BS-MSP）, reverse transcription-PCR （RT-PCR） and immunohistochemistry were respectively used to detect the methylation status, mRNA expression and protein expression of Gadd45G in ESCC tissues and the corresponding adjacent non-cancerous tissues. Furthermore, the associations of the aberrant methylation and expression of Gadd45G gene with the clinicopathological characteristics of patients with ESCC were analyzed. Results： The methylation frequency of distal promoter （region 1） of Gadd45G gene in ESCC tissues （4.7%, 6/128） was significantly higher than that in the corresponding adjacent non- cancerous tissues （0.0%, 0/128） （P 〈 0.05）. The mRNA and protein expressions of Gadd45G in ESCC tissues with distal promoter methylation were not significantly different from those in ESCC tissues without distal promoter methylation （P 〉 0.05）. The methylation frequencies of proximal promoter andexon 1 of Gadd45G gene （region 2 and region 3） in ESCC tissues （45.3%, 58/128） were both significantly increased in comparison with those in the corresponding adjacent non-cancerous tissues （0.0%, 0/128） （P 〈 0.01）. The methylation status of proximal promoter and exon 1 of Gadd45G gene in HCC tissues was associated with TNM stage and pathological differentiation （P 〈 0.05）. The mRNA and protein expressions of Gadd45G in ESCC tissues were significantly decreased in comparison with those in the corresponding adjacent non-cancerous tissues （P 〈 0.05）, and which were also associated with TNM stage, pathological differentiation and methylation status of proximal promoter and exon 1 of Gadd45G gene （P 〈 0.05）. Conclusion： The expression of Gadd45G is decreased by hypermethylatio

关 键 词：食管肿瘤 癌 鳞状细胞 DNA甲基化 基因表达 Gadd45G 

分 类 号：R735.1[医药卫生—肿瘤]