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

• Published in: Clinical cancer research Vol. 13; no. 24; pp. 7296 - 7304
• Main Authors: Yu, Jian, Zhu, Tongyu, Wang, Zhirou, Zhang, Hongyu, Qian, Ziliang, Xu, Huili, Gao, Baomei, Wang, Wei, Gu, Lianping, Meng, Jun, Wang, Jina, Feng, Xu, Li, Yixue, Yao, Xuebiao, Zhu, Jingde
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-12-2007
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Base Sequence; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - urine; bladder cancer; DNA Methylation; Female; gene cluster; Humans; Male; Medical sciences; Methylation specific PCR; Middle Aged; Molecular Sequence Data; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; Polymerase Chain Reaction; ROC Curve; Sensitivity and Specificity; Tumors of the urinary system; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - urine; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; urine sediments; Urine; Biological fluid; Urinary system disease; Genetic marker; Bladder disease; Urinary tract disease; Malignant tumor; Diagnosis; Detection; Methylation; Bladder cancer; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-07-0861

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 American and Chinese cases.
Conclusions: Methylation profiling of an 11-gene set in urine sediments provides a sensitive and specific detection of bladder cancer.