贲门腺癌中GADD45G基因的异常甲基化及表达  

Aberrant Methylation and Expression of Growth Arrest and DNA-Damage-Inducible 45G Gene in Gastric Cardia Adenocarcinoma

作　　者：游庆朋[1] 郭炜[2] 张明慧[2] 崔蕾[2] 董稚明[2] 

机构地区：[1]河北省邢台市人民医院病理科,054001 [2]河北医科大学第四医院河北省肿瘤研究所病理研究室

出　　处：《天津医药》2013年第10期949-952,I0001,共5页Tianjin Medical Journal

基　　金：国家自然科学基金资助项目(项目编号:81101854);河北省科技厅科技支撑课题(项目编号:072761223)

摘　　要：目的探讨生长阻滞和DNA损伤诱导基因G(GADD45G)在贲门腺癌(GCA)中的异常甲基化及表达。方法分别应用亚硫酸氢盐转换-甲基化特异性PCR(BS-MSP)方法及免疫组织化学的方法检测138例贲门癌及相应的癌旁正常组织中GADD45G基因的甲基化及蛋白表达情况。结果贲门腺癌及癌旁组织中均未检测到GADD45G远端启动子区即位点1(region 1)甲基化。GADD45G第2个CpG岛的近端启动子区及第1外显子区即位点2和位点3(region 2/3)在贲门腺癌及癌旁组织中的甲基化率相同,均为49.3%(68/138),高于癌旁正常组织(0),差异有统计学意义,且此2个区域的甲基化率在Ⅲ期和Ⅳ期贲门腺癌中明显增高(P<0.05)。贲门腺癌癌组织中GADD45G的蛋白表达阳性率为35.5%(49/138)显著低于癌旁正常组织的蛋白表达率82.6%(114/138),差异有统计学意义(P<0.05),且与其近端启动子区及第1外显子区的甲基化状态之间呈负相关(rs=-0.398)。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的基因沉默可能是贲门腺癌中此基因表达降低的机制之一。Objective To investigate the aberrant methylation and expression of growth arrest and DNA-damage-in- ducible 45 gamma （GADD45G） gene in gastric cardia adenocarcinoma （GCA）. Methods Bisulfite conversion-methylation specific polymerase chain reaction method （BS-MSP） and immunohistochemistry method were used respectively to detect the methylation status and protein expression of GADD45G in 138 GCA tumor tissues and corresponding normal tissues. Re- sults The methylation status of GADD45G distal promoter （region l） was not detected in GCA tumor tissues and corre- sponding normal tissues. For GADD45G region 2 and region 3, the BS-MSP results of region 3 were identical to that of re- gion 2. The methylation frequency of proximal promoter and exon 1 in GADD45G is｜and 2 （region 2 and region 3） in GCA tu- mor tissues （49.3%, 68/138） was significantly increased compared to that in corresponding normal tissues （0, P 〈 0.01）. The methylation status of this two sites in tumor tissues was associated with TNM stage of tumors （P 〈 0.05）. The protein expres- sion of GADD45G in tumor tissues was significantly decreased than that in corresponding normal tissues （P 〈 0.05）, and threre was a significant negative correlation with methylation status of GADD45G proximal promoter and exon 1 （r=-0.398）. Conclusion The decreased expression of GADD45G by hypermethylation of proximal promoter exon 1 of the gene may play an important role in gastric cardia adenocarcinoma.

关 键 词：贲门 腺癌 外显子 DNA甲基化 免疫组织化学 生长阻滞和DNA损伤诱导基因G 

分 类 号：R818.02[医药卫生—放射医学]