Genomics

Dataset Information

238

Identification of a novel set of DNA methylation markers in bladder cancer using MBD-methylCap/seq and urine DNA screening in a Chinese population


ABSTRACT: The aim of the present study was to identify novel DNA methylation markers in bladder cancer (BCa) through genome-wide profiling of bladder cancer cell lines and subsequent MSP screening in urine samples. Experimental Design: MBD methylCap/seq was carried out to screen differentially methylated CpG islands using two BCa cell lines (5637 and T24) and two normal bladder mucosa (BM) samples. The top one hundred most hypermethylated targets were screened using Methylation Specific PCR (MSP) in small and big cohort of urine samples from BCa patients and normal controls. The diagnostic performance of the gene panel was further evaluated in different clinical scenarios. Results: In total, 1,627 gene promoter regions hypermethylated in BCa cell line were identified in genomic level methylation profiling. The followed screening procedure in clinical urine sample generated eight genes (VAX1, KCNV1, ECEL1, TMEM26, TAL1, PROX1, SLC6A20, and LMX1A) capable of differentiating BCa from normal control. Subsequent validation in a large sample size enabled the optimisation of 5 methylation targets (VAX1, KCNV1, TAL1, PPOX1 and CFTR) for BCa diagnosis with sensitivity and specificity of 86.32% and 87.13%, respectively. In addition, VAX1 and LMX1A methylation could predict the tumour recurrence. Conclusions: Tumor specific biomarkers of BCa could be established by first performing genome level methylation profiling with cell lines and then screening the potential targets in urine samples. The panel of methylated genes identified was promising for the early non-invasive detection and surveillance of BCa. MBD methylCap/seq was carried out to screen differentially methylated CpG islands using two BCa cell lines (5637 and T24), and two normal bladder tissue mix as control.

ORGANISM(S): Homo sapiens  

SUBMITTER: Jian Yu   Shi-Cheng Guo  Yang-Xing Zhao  jian yu 

PROVIDER: E-GEOD-33839 | ArrayExpress | 2012-04-30

SECONDARY ACCESSION(S): SRP009396GSE33839PRJNA148095

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Methylcap-seq reveals novel DNA methylation markers for the diagnosis and recurrence prediction of bladder cancer in a Chinese population.

Zhao Yangxing Y   Guo Shicheng S   Sun Jinfeng J   Huang Zhaohui Z   Zhu Tongyu T   Zhang Hongyu H   Gu Jun J   He Yinghua Y   Wang Wei W   Ma Kelong K   Wang Jina J   Yu Jian J  

PloS one 20120417 4


PURPOSE: There is a need to supplement or supplant the conventional diagnostic tools, namely, cystoscopy and B-type ultrasound, for bladder cancer (BC). We aimed to identify novel DNA methylation markers for BC through genome-wide profiling of BC cell lines and subsequent methylation-specific PCR (MSP) screening of clinical urine samples. EXPERIMENTAL DESIGN: The methyl-DNA binding domain (MBD) capture technique, methylCap/seq, was performed to screen for specific hypermethylated CpG islands in  ...[more]

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