摘要
目的:检测食管鳞状细胞癌(ESCC)中Wnt通路拮抗基因家族分泌型卷曲相关蛋白(SFRP)基因的甲基化状态,探讨其与食管鳞癌发生的关系。方法:应用甲基化特异性PCR(MS-PCR)及RT-PCR的方法检测78例食管鳞癌及相应癌旁非肿瘤组织中SFRP1、SFRP2、SFRP4和SFRP5基因的甲基化状态及mRNA表达情况,并分析其与Wnt通路中心因子β-catenin蛋白表达的关系。结果:在食管鳞癌组织中,SFRP1、SFRP2、SFRP4和SFRP5基因的甲基化率分别为65.4%(51/78)、69.2%(54/78)、62.8%(49/78)和52.6%(41/78),均明显高于癌旁非肿瘤组织(P<0.01)。这4个基因的甲基化率与肿瘤患者的组织学分级及临床分期均无关,但它们共同发生甲基化的频率则与临床分期显著相关(P<0.05)。这4个基因mRNA的阳性表达率分别为42.3%(33/78)、46.2%(36/78)、50.0%(39/78)和39.7%(31/78),均明显低于癌旁非肿瘤组织(P<0.01)。在发生甲基化的食管癌组织中这4个基因的mRNA表达阳性率及β-catenin蛋白的异质表达率均明显低于未发生甲基化的癌组织,且差异显著(P<0.05)。结论:食管鳞癌组织中SFRP1、SFRP2、SFRP4和SFRP5基因均呈高甲基化状态,并有可能通过Wnt/β-catenin信号转导通路参与了食管癌的发生。联合检测SFRP基因家族甲基化状态对于食管癌的预后判断有一定指导意义。
AIM： To investigate the promoter methylation of secreted frizzled - related protein（SFRP） genes in esophageal squamous cell cancer（ESCC）. METHODS： The methods of methylation- specific PCR（ MS- PCR） and RT - PCR were applied to examine the CpG methylation of the SFRP promoter and the mRNA expression of SFRP genes, respectively, in 78 samples of ESCC and corresponding adjacent non - cancer tissues. The protein expression of β - catenin was determined by immunohistochemistry. RESULTS： In the ESCC tissues, the frequencies of promoter methylation in SFRP1, SFRP2, SFRP4 and SFRP5 genes were 65. 4% （51/78）, 69. 2% （54/78）, 62. 8% （49/78） and 52. 6% （41/ 78）, respectively, significantly higher than those in the adjacent tissues （ P 〈 0. 01 ）. The hypermethylation of these genes had no correlation with clinical stage and pathological classification in ESCC tissues（ P 〉 0. 05 ）. The frequency of simulta- neous methylation of the 4 genes was correlated with the clinical stage（P 〈 0. 05 ）. The positive rates of mRNA expression of the 4 genes in ESCC tissues were 42. 3% （33/78）, 46. 2% （36/78）, 50. 0% （39/78） and 39. 7% （31/78）, respectively lower than those in the adjacent tissues（ P 〈 0. 01 ）. The mRNA expression of SFRP genes and the ectopic expression of 13 - catenin were correlated with the methylation frequency of SFRP genes （P 〈 0. 01 ）. CONCLUSION： Promoter methylation of SFRP1, SFRP2, SFRP4 and SFRP5 genes was a frequent event in ESCC, indicating a contribution to the patho- genesis of ESCC through aberrant canonical Wnt/β - catenin signaling pathway. Combination analysis of methylation status in SFRP genes may has definite value on estimating prognosis of ESCC.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2011年第2期278-283,共6页
Chinese Journal of Pathophysiology
基金
河北省医学科学研究重点课题计划资助项目(No.20090466)
关键词
食管肿瘤
甲基化
分泌型卷曲相关蛋白
WNT通路
Esophageal neoplasms
Methylation
Secreted frizzled - related protein
Wnt pathway
