膀胱癌组织中肺癌肿瘤抑制物1基因启动子甲基化状态和蛋白表达及其临床意义  

Methylation status and protein expression of promoter of tumor suppressor in lung cancer 1 gene in bladder cancer and their clinical significance

作　　者：杨永姣 刘莉[2] 陈业刚[1] 王尚任 刘晓强[1] 陈少峰[1] 孙光[1] 

机构地区：[1]天津医科大学第二医院泌尿外科,天津300211 [2]天津市泌尿外科研究所,天津300211

出　　处：《中国现代医学杂志》2015年第23期35-39,共5页China Journal of Modern Medicine

基　　金：天津市科委自然科学基金重点项目(No:12JCZDJC23700)

摘　　要：目的探讨膀胱尿路上皮癌组织中肺癌肿瘤抑制物1(TSLC1)基因启动子区Cp G岛甲基化状态和蛋白的表达,及其与临床病理参数的关系。方法分别采用甲基化特异性PCR(MSP)和Western blot检测84例膀胱尿路上皮癌组织和20例正常膀胱黏膜组织中TSLC1基因启动子Cp G岛甲基化状态和蛋白表达。结果20例正常膀胱黏膜组织中均未检测到TSLC1基因甲基化,84例膀胱尿路上皮癌组织中43例检测到TSLC1启动子区甲基化,甲基化率为51.2%,两组比较差异有统计学意义(P<0.01);膀胱癌组织中TSLC1基因启动子区Cp G岛甲基化状态与患者的年龄、性别、肿瘤数目无关(P>0.05),而与肿瘤直径、肿瘤是否复发、病理分级和临床分期有关,差异有统计学意义(P<0.05)。膀胱癌组织中TSLC1蛋白表达[(0.261 3±0.140 5)]较正常组织[(0.695 7±0.092 4)]显著下降,差异有统计学意义(P<0.01)。膀胱癌组织中发生TSLC1基因启动子Cp G岛甲基化的TSLC1蛋白表达[(0.114 3±0.044 3)]明显低于未发生TSLC1基因启动子Cp G岛甲基化[(0.375 6±0.043 9)],差异有统计学意义(P<0.01)。结论 TSLC1基因启动子Cp G岛甲基化与膀胱癌的发生、发展相关,TSLC1基因启动子Cp G岛甲基化可能是导致其蛋白表达下调的主要原因之一。[Objective] To investigate the methylation status of CpG island of tumor suppressor in lung cancer 1 （TSLC1） gene promoter and the expression of TSLC1 protein in bladder urothelium carcinoma, as well as to investigate their associations with the clinicopathological characteristics of patients with bladder urothelium carcinoma. [Methods] The methylation status of CpG island of TSLC1 gene and TSLC1 protein expression level in the bladder urothelium carcinoma tissue of 84 cases and the normal bladder mucous tissue of 20 cases were measured by methylation specific PCR （MSP） and Western blot. [Results] No TSLC1 gene methylation was detected in the normal bladder mucous tissue of the 20 cases, while TSLC1 promoter methylation was found in the bladder urothelium carcinoma tissue of the 43/84 cases, the methylation rate was 51.2%, and the difference was significant between the normal bladder mucous group and the bladder cancer group （P〈 0.01）. The methylation of TSLCI gene promoter in the bladder urothelium carcinoma tissue did not correlate with the patient＇s age, gender or tumor number （P〉 0.05）, while had correlations with tumor diameter, tumor recurrence, pathology classification and clinical stage （P〈 0.05）. The TSLC1 protein level in the fresh bladder urothelium carcinoma tissue was lower than that in the normal bladder mucous tissue [（0.2613 ±0.1405） vs （0.6957 ± 0.0924）], the difference was statistically significant （P〈 0.01）. The tumor tissue with TSLC1 gene promoter CpG island methylation showed a lower expression of TSLC1 protein than the unmethylation tumor tissue [（0.1143 ± 0.0443） vs （0.3756 ± 0.0439）] in the bladder cancer patients, the difference was statistically significant （P〈 0.01）. [Conclusion] Methylation of CpG island of TSLC1 gene promoter is closely correlated with the occurrence and development of bladder urothelium carcinoma. It may be one of the main reasons for the down-regulation of TSLC1 protein expression.

关 键 词：膀胱癌 肺癌肿瘤抑制因子1 甲基化 

分 类 号：R737.14[医药卫生—肿瘤]