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目的:寻找并评估通过对尿沉淀细胞DNA甲基化分析检出膀胱癌的基因组合。方法:甲基化特异性PCR(methylation specific polymerase chain reaction,MSP)。结果:对3株膀胱癌细胞系进行的20个基因启动子区域CpG岛甲基化状态分析发现,除BRCA1以外其他基因至少在细胞株的1个等位基因呈高甲基化状态。对40例膀胱癌组和3组非膀胱癌对照组的尿沉淀细胞DNA进行了6个基因甲基化状态分析发现,SALL3在膀胱癌组甲基化率为67.5%(27/40),MT1A为50.0%(20/40),HPP1为50.0%(20/40),MYOD1为37.5%(15/40),BRCA1为32.5%(13/40),TMS1为5.0%(2/40)。这6个基因在3个非膀胱癌对照组,即非肿瘤性泌尿生殖系统疾病患者23例、脑外科患者6例和正常人群7例均呈去甲基化状态,所以可以受试基因中任一个基因呈现高甲基化状态作为膀胱癌的指征,该法检出膀胱癌的敏感性为90.0%(36/40)。结论:对这5个基因在尿沉淀细胞DNA中甲基化状态的检测可望有效地检出膀胱癌。
OBJECTIVE: To search for and assess the genetic association of bladder cancer detected by DNA methylation analysis of urine sediment cells. Methods: Methylation specific polymerase chain reaction (MSP). Results: Methylation status of CpG islands in 20 promoter regions of 3 bladder cancer cell lines showed that all genes except BRCA1 were hypermethylated in at least one allele of cell line. The methylation status of urine sediment in 40 bladder cancer patients and 3 non-bladder cancer control subjects was analyzed by methylation status. The methylation rates of SALL3 in bladder cancer were 67.5% (27/40), MT1A Was 50.0% (20/40), HPP1 was 50.0% (20/40), MYOD1 was 37.5% (15/40), BRCA1 was 32.5% (13/40) and TMS1 was 5.0% (2/40). These six genes were demethylated in three non-bladder cancer control groups, 23 patients with non-neoplastic genitourinary diseases, 6 patients with brain surgery, and 7 normal individuals. Therefore, A gene is hypermethylated as an indication of bladder cancer, which detected bladder cancer with a sensitivity of 90.0% (36/40). Conclusion: The detection of methylation status of these five genes in urine sediment cells is expected to detect bladder cancer effectively.