A novel set of DNA methylation markers in urine sediments for sensitive/specific detection of bladder cancer
A novel set of DNA methylation markers in urine sediments for sensitive/specific detection of bladder cancer
复制标题
尿液沉积物中的一组新型 DNA 甲基化标记物用于膀胱癌的灵敏/特异性检测
DOI：
10.1158/1078-0432.ccr-07-0861
复制
发表时间：
2007-12-15
影响因子：
11.5
通讯作者：
Zhu, Jingde
中科院分区：
文献类型：
--
作者：
Yu, Jian;Zhu, Tongyu;Zhu, Jingde
目的：本研究的目的是提供一个更好的尿沉渣中的DNA甲基化标志物的敏感性和特异性检测膀胱cancer.Experimental设计：五十九个肿瘤相关基因进行了分析，在三个膀胱癌细胞系，一个小队列的癌症活检和尿沉渣甲基化特异性PCR。然后在132名膀胱癌患者的尿沉渣中分析了21个候选基因（0a期8例，1期68例，11期50例，111期4例，IV期2例），23例年龄匹配的非癌性泌尿系病变患者，6例神经系统疾病患者，7例健康志愿者。尽管在23例非癌性泌尿系病变患者中有3例报告了4个基因的6次甲基化，但在尿沉渣中报告了15个基因的癌症特异性高甲基化（P < 0.05）。对11个基因集（SALL3、CFTR、ABCC 6、HPR 1、RASSF1A、MT1A RUNX3、ITGA 4、BCL 2、ALX4、MYOD 1、DRM、CDH13、BMP 3B、CCNA 1、RRRM、MINT 1和BRCA 1）的甲基化评估证实了132例膀胱癌病例中121例的现有诊断（敏感性，91.7%），准确率为87%。值得注意的是，超过75%的0a期和88%的I期疾病被检测到，表明其在膀胱癌早期诊断中的价值。有趣的是，在美国使用的甲基化标记的集群报告膀胱癌是明显不同的，在这项研究中确定的，这表明美国和中国cases.Conclusions之间可能存在表观遗传差异：尿沉渣中的11个基因组的甲基化分析提供了一个敏感和特异性的检测膀胱癌。
Purpose: This study aims to provide a better set of DNA methylation markers in urine sediments for sensitive and specific detection of bladder cancer.Experimental Design: Fifty-nine tumor-associated genes were profiled in three bladder cancer cell lines, a small cohort of cancer biopsies and urine sediments by methylation-specific PCR. Twenty-one candidate genes were then profiled in urine sediments from 132 bladder cancer patients (8 cases for stage 0a; 68 cases for stage 1; 50 cases for stage 11; 4 cases for stages 111; and 2 cases for stage IV), 23 age-matched patients with noncancerous urinary lesions, 6 neurologic diseases, and 7 healthy volunteers.Results: Despite six incidences of four genes reported in 3 of 23 noncancerous urinary lesion patients analyzed, cancer-specific hypermethylation in urine sediments were reported for 15 genes (P < 0.05). Methylation assessment of an 11-gene set (SALL3, CFTR, ABCC6, HPR1, RASSF1A, MT1A RUNX3, ITGA4, BCL2, ALX4, MYOD1, DRM, CDH13, BMP3B, CCNA1, RPRM, MINT1, and BRCA1) confirmed the existing diagnosis of 121 among 132 bladder cancer cases (sensitivity, 91.7%) with 87% accuracy. Significantly, more than 75% of stage 0a and 88% of stage I disease were detected, indicating its value in the early diagnosis of bladder cancer. Interestingly, the cluster of reported methylation markers used in the U.S. bladder cancers is distinctly different from that identified in this study, suggesting a possible epigenetic disparity between the American and Chinese cases.Conclusions: Methylation profiling of an 11-gene set in urine sediments provides a sensitive and specific detection of bladder cancer.