贲门腺癌中TGF-β1型受体启动子区甲基化状态分析  

Promoter Methylation of Transforming Growth Factor-beta Receptor Type 1 Gene and Expression of TGF-β1 in Gastric Cardia Adenocarcinoma

作　　者：郭炜[1] 郭艳丽[1] 杨植彬[1] 邝钢[1] 乔义岭 董稚明[1] 

机构地区：[1]河北医科大学第四医院河北省肿瘤研究所,石家庄050011 [2]河北省优抚医院医务处

出　　处：《肿瘤防治研究》2011年第5期524-527,共4页Cancer Research on Prevention and Treatment

基　　金：河北省医学科学研究重点课题计划资助项目(20090465)

摘　　要：目的探讨贲门腺癌(gastric cardia adenocarcinoma,GCA)中TGF-β1型受体(transforminggrowth factor-beta receptor type 1 gene,TGFBR1)启动子区的甲基化状态及其与TGF-β1蛋白表达之间的相关性。方法分别应用甲基化特异性PCR(MSP)方法、RT-PCR方法和免疫组织化学法检测贲门腺癌组织及相应癌旁组织的TGFBR1甲基化情况、mRNA和蛋白表达情况,应用免疫组织化学法检测相应TGF-β1的蛋白表达情况。结果 TGFBR1在贲门腺癌组织的甲基化率为30.9%(34/110),显著高于癌旁正常组织(P<0.01)。Ⅲ期和Ⅳ期贲门癌患者中TGFBR1基因发生甲基化的比率显著高于Ⅰ期和Ⅱ期患者(P<0.05)。贲门癌组织中TGFBR1基因的mRNA及蛋白表达显著低于癌旁正常组织(P<0.05)且与其甲基化状态之间有明显的相关性。TGF-β1在贲门癌组织中的表达(65.5%)明显升高,与相应癌旁正常组织相比差异有统计学意义(P<0.01),且随肿瘤分期的增高和肿瘤分化程度的降低,TGF-β1的阳性表达率明显升高(P<0.05)。TGFBR1和TGF-β1蛋白在贲门腺癌中的表达呈明显的负相关。结论 TGF-β1型受体基因启动子区的高甲基化及其TGF-β1的过表达可能参与了贲门腺癌的发生发展过程,TGF-β1型受体基因启动子区发生甲基化导致的基因沉默可能是贲门腺癌发生的机制之一。Objective To investigated the relationships between the promoter methylation of transforming growth factor-beta receptor type 1 gene（TGFBR1）and protein expression of TGF-β1 and gastric cardia adenocarcinoma（GCA）.Methods MSP approach,RT-PCR and immunohistochemistry methods were used respectively to examine the methylation status of the 5＇ CpG island,mRNA and protein expression of TGFBR1 and TGF-β1 in tumors and corresponding normal tissues.Results The prevalence TGFBR1 methylation was 34 /110（30.9%） in tumor specimens,and significantly higher than that in corresponding normal tissues（P0.01）.Methylation frequencies of stage Ⅲ and Ⅳ tumor tissues were significantly higher than those in stageⅠandⅡtumor tissues（P0.05）.TGFBR1 mRNA and protein expression of tumor tissues were significantly lower than that in corresponding normal tissues and was correlated with its methylation status.72/110（65.5%） tumor tissues were demonstrated positive immunostaining of TGF-β1 and the frequency of positive protein expression of TGF-β1 was significantly higher than that in corresponding normal tissues（P0.01）.The protein expression of TGF-β1 was significantly different among three differentiation groups of GCA（P0.05）.The protein expression of TGFBR1 was inversely correlated with TGF-β1 in GCA.Conclusion Promoter hypermethylation of TGFBR1 and the higher protein expression of TGF-β1 might play important roles in gastric cardia adenocarcinoma.

关 键 词：贲门腺癌 DNA甲基化 TGF-β1型受体 TGF-Β1基因 

分 类 号：R735.2[医药卫生—肿瘤]