A Novel Set of DNA Methylation Markers in Urine Sediments for Sensitive/Specific Detection of Bladder Cancer

作者：Jian Qing Yu, Tongyu Zhu, Zhirou Wang, Hongyu Zhang, Ziliang Qian, Huili Xu, Baomei Gao, Wei Qiang Wang, Lianping Gu, Jun Meng, Jina Wang, Feng Xu, Yixue Li, Xuebiao Yao, Jingde Zhu · 发表于：Clinical Cancer Research · 年份：2007 · DOI：10.1158/1078-0432.ccr-07-0861 · 被引用次数：207 · 研究领域：Bladder and Urothelial Cancer Treatments、Epigenetics and DNA Methylation、Ferroptosis and cancer prognosis

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 I; 50 cases for stage II; 4 cases for stages III; 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 Am...