膀胱肿瘤组织及尿液标本中TWIST1基因的甲基化水平研究  

Hypermethylation of TWIST1 gene in tumor tissues and voided urine in bladder cancer patients

作　　者：姜凤全 杨春[2] 陈阵[1] 

机构地区：[1]大连医科大学附属第一医院检验科,辽宁大连116011 [2]大连医科大学附属第一医院核医学科,辽宁大连116011

出　　处：《中国癌症杂志》2014年第3期161-165,共5页China Oncology

基　　金：辽宁省科技厅基金项目(No:2013225021)

摘　　要：背景与目的:众多遗传学及表观遗传性的改变引发癌基因的激活剂抑癌基因的失活是膀胱肿瘤发生、发展的重要原因,本研究旨在揭示膀胱肿瘤患者肿瘤组织及尿液标本TWIST1基因的甲基化模式。方法:78例经病理确诊的膀胱肿瘤标本、癌旁正常组织及配对75例尿液标本组成实验组,75例年龄及性别比例匹配的非肿瘤个体组成对照组。从肿瘤、癌旁及尿液标本提取DNA,甲基化特异性聚合酶链反应(methylationspecific polymerase chain reaction,MSP)检测肿瘤组织、癌旁组织及尿液标本中TWIST1基因的甲基化水平,检测结果与尿细胞学检测结果进行对比,比较两种检测方法的灵敏度及特异度。结果:甲基化检测结果显示,88.5%的肿瘤标本及84.0%的尿液标本出现TWIST1基因的甲基化,11.5%的癌旁正常组织及5.3%的对照尿液标本出现甲基化。尿细胞学检测结果显示,49.3%的肿瘤患者尿液标本检测出瘤细胞,17.3%的对照者被诊断为肿瘤或疑似肿瘤。尿液标本甲基化检测灵敏度及特异度显著高于尿细胞学检测方法。针对低级别肿瘤,TWIST1基因甲基化检测灵敏度为66.7%,高于尿细胞学检测(33.3%)。结论:TWIST1基因甲基化水平检测可作为一种简单、非侵入、敏感及特异的方法应用于早期膀胱肿瘤诊断筛查。Background and purpose： Accumulation of genetic and epigenetic changes that lead to the activation of proto-oncogenes or inactivation of tumor suppressor genes play important roles in development and progression of bladder cancer. We aimed to investigate the methylation patterns of TWIST! gene in bladder cancer. Methods： A total number of 78 histologically confirmed bladder tumor samples and paired 75 urine samples constituted the study group and was compared with 75 age-matched and gender-matched non-cancerous individuals. DNA was purified from both tumor, adjacent tissues and urine samples. The methylation status of the TWIST1 gene was analyzed by methylation-specific polymerase chain reaction （MSP） in both urinary bladder cell carcinoma samples, adjacent tissues and urine samples. Sensitivity and specificity values of the method were assessed and compared with the results of the cytology test. Results： Methylation of TWIST1 was detected in 88.5% of carcinoma samples and 84% of the paired urine samples, respectively; 11.5% carcinoma adjacent tissues and 5.3% control urine sample was methylated. The sensitivity by urine cytology detection method was 49.3% in in bladder cancer patients, and was 17.3% in control group. The sensitivity of TWIST1 genes was 66.7% for low-grade cases. The sensitivity of urine cytology was 33.3% for the same low-grade cases. Conclusion： The methylation analysis of TWIST1 geue may be a simple, non-invasive, sensitive, and specific method for early detecting bladder cancer cells in urine.

关 键 词：TWIST1基因 膀胱肿瘤 尿细胞学检测 甲基化 

分 类 号：R737.14[医药卫生—肿瘤]