天津医药

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贲门腺癌中GADD45G基因的异常甲基化及表达

游庆朋1,郭炜2,张明慧3,崔蕾3,董稚明3   

  1. 1. 河北省邢台市人民医院病理科
    2. 河北医科大学第四医院 河北省肿瘤研究所病理研究室
    3. 河北医科大学第四医院,河北省肿瘤研究所病理研究室
  • 收稿日期:2012-12-18 修回日期:2013-05-08 出版日期:2013-10-15 发布日期:2013-10-15
  • 通讯作者: 董稚明

Aberrant Methylation and Expression of Growth Arrest and DNA-Damage-Inducible45G Gene in Gastric Cardia Adenocarcinoma

YOU Qing peng1,GUO Wei 2,ZHANG Ming hui2,CUI Lei 3,DONG Zhi ming4   

  1. 1. Xingtai People's Hospital of Hebei Province
    2. Fourth Hospital of Hebei Medical University Hebei Cancer Institute
    3. Fourth Hospital of Hebei Medical UniversityHebei Cancer Institute,
    4. Fourth Hospital of Hebei Medical University,Hebei Cancer Institute
  • Received:2012-12-18 Revised:2013-05-08 Published:2013-10-15 Online:2013-10-15
  • Contact: DONG Zhi ming

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摘要：

 【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（region1）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（region2/3）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。

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

Abstract:

[Abstract]   Objective  To investigate the aberrant methylation and expression of growth arrest and DNA-damage-in- ducible45gamma (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 in138GCA tumor tissues and corresponding normal tissues.  Results  The methylation status of GADD45G distal promoter (region1) was not detected in GCA tumor tissues and corresponding normal tissues. For GADD45G region2and region3, the BS-MSP results of region 3were identical to that of region2. The methylation frequency of proximal promoter and exon 1in GADD45G island2(region2and region3) in GCA tumor 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 expression 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 exon1(rs=-0.398).  Conclusion   Thedecreased expression of GADD45G by hypermethylation of proximal promoter exon1of the gene may play an important role in gastric cardia adenocarcinoma.

Key words: cardia, adenocarcinoma, exons, DNA methylation, immunohistochemistry, growth arrest and DNA-damage-inducible 45 gamma