A novel set of DNA methylation markers in urine sediments for sensitive/specific detection of bladder cancer.
OBJECTIVE
This study aims to provide a better set of DNA methylation markers in urine sediments for sensitive and specific detection of bladder cancer.


METHODS
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.
Yu
Jian
J
Cancer Genetics and Gene Therapy Program, The State Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, China.
Zhu
Tongyu
T
Wang
Zhirou
Z
Zhang
Hongyu
H
Qian
Ziliang
Z
Xu
Huili
H
Gao
Baomei
B
Wang
Wei
W
Gu
Lianping
L
Meng
Jun
J
Wang
Jina
J
Feng
Xu
X
Li
Yixue
Y
Yao
Xuebiao
X
Zhu
Jingde
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012372:ROC Curve; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000652:urine*
D014408:Biomarkers, Tumor