T-cadherin启动子甲基化与胃癌恶性生物学行为及预后关系的研究  

Methylation of T-cadherin promoter is associated with malignant biological behavior and prognosis in gastric cancer

作　　者：吕昊玥 曹伟[1] 赵军莉[1] 宋鉴清[1] 

机构地区：[1]中国医科大学附属第一医院检验科,辽宁沈阳110001

出　　处：《现代肿瘤医学》2014年第7期1618-1623,共6页Journal of Modern Oncology

基　　金：辽宁省自然科学基金资助项目(编号:201102291)

摘　　要：目的:探讨T-cadherin基因表达及启动子甲基化与胃癌恶性生物学行为及预后的相关性。方法:采用免疫组织化学法(IHC)和甲基化特异性PCR法(MSP)检测80例临床手术切除的胃癌标本及40例相应癌旁组织标本中T-cadherin表达及启动子甲基化情况,并与临床病理资料进行对照分析,每例患者随访24个月。结果:80例胃癌标本中,T-cadherin阳性表达率仅为45.0%(36/80),与相应癌旁组织相比明显减低。T-cadherin表达与组织分型(P=0.032)、肿瘤分化程度(P=0.037)、是否存在淋巴结转移(P=0.010)及TNM分期有关(P=0.000),与患者年龄、性别及肿瘤大小无关(P>0.05)。80例胃癌标本中有38例存在T-cadherin启动子甲基化现象(47.5%),癌旁组织标本则全部呈非甲基化状态(100.0%)。T-cadherin启动子甲基化与组织分型(P=0.012)、肿瘤分化程度(P=0.020)、是否存在淋巴结转移(P=0.020)及TNM分期有关(P=0.007),与患者年龄、性别及肿瘤大小无关(P>0.050)。24个月的随访结果显示:T-cadherin启动子甲基化组的平均生存时间和中位生存时间均较非甲基化组缩短,两组差异有统计学意义(P=0.029)。通过Cox比例风险模型评估,胃癌的分化程度(P=0.030)、是否存在淋巴结转移(P=0.010)及TNM分期(P=0.010)均可影响患者的生存时间,分化程度低、发生淋巴结转移、TNM分期Ⅲ-Ⅳ期的胃癌患者死亡风险增加。结论:T-cadherin启动子甲基化是导致该蛋白表达下调的原因之一,与胃癌恶性生物学行为及预后密切相关,可作为胃癌恶性程度判断及预后评估的参考指标,对指导临床诊治有重要意义。Objective： To investigate the expression status and aberrant methylation of T - cadherin and the associ- ation with malignant biological behavior and prognosis in gastric cancer. Methods： Expression status of T - cadherin was detected in a total of 80 surgical specimens of gastric cancer and 40 corresponding normal gastric tissues by im- munohistochemistry. The methylation status of T - cadherin promoter was observed under methylation specific PCR （MSP） in above specimens. Then compared with the clinical pathological data. Patients were followed up for 24 months. Results ：The expression rate of T - cadherin was only 45.0% in 80 gastric cancer specimens（36/80）. It was significantly reduced in tumor tissue samples, compared with the adjacent normal gastric tissue samples. The expres- sion of T - cadherin was associated significantly with clinical characters, such as gross type （ P = 0.032 ）, differentia- tion（P =0.037） ,lymph node metastasis（P =0.010） and TNM stage（P =0.000）. No correlation was found between T- cadherin expression and age, sex or tumor size （P 〉 O. 050）. T -cadherin methylation was observed in 38 of 80 gastric cancer tissues （47.5 % ）. Conversely, only unmethylated PCR amplification products showed in adjacent normal gastric tissue samples（ 100.0% ）. The methylation status of T - cadherin promoter was associated significantly with clinical characters, such as gross type （P = 0.012 ）, differentiation （ P = 0. 020）, lymph node metastasis （ P = 0. 020 ） and TNM stage （ P = 0. 007 ）. No correlation was found between T - cadherin promoter methylation and age, sex or tumor size （P 〉 0.05 ）. The follow - up of 24 months showed that the group with methylated T - cadherin had shorter mean survival time and median survival time than the group with unmethylated T - cadherin. This difference was sta- tistically significant（ P =0. 029 ）. In the Cox proportional hazards model analysis, the differentiation（ P = 0. 030）, lymph node metastasi

关 键 词：胃癌 T-钙黏蛋白 甲基化 免疫组化 生存时间 预后 

分 类 号：R735.2[医药卫生—肿瘤]