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

<h4>Purpose</h4>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 methylat...

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Autores principales:	Yangxing Zhao, Shicheng Guo, Jinfeng Sun, Zhaohui Huang, Tongyu Zhu, Hongyu Zhang, Jun Gu, Yinghua He, Wei Wang, Kelong Ma, Jina Wang, Jian Yu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d330ac05113f4386a57323857de25dc5
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spelling	oai:doaj.org-article:d330ac05113f4386a57323857de25dc52021-11-18T07:21:56ZMethylcap-seq reveals novel DNA methylation markers for the diagnosis and recurrence prediction of bladder cancer in a Chinese population.1932-620310.1371/journal.pone.0035175https://doaj.org/article/d330ac05113f4386a57323857de25dc52012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22529986/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Purpose</h4>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.<h4>Experimental design</h4>The methyl-DNA binding domain (MBD) capture technique, methylCap/seq, was performed to screen for specific hypermethylated CpG islands in two BC cell lines (5637 and T24). The top one hundred hypermethylated targets were sequentially screened by MSP in urine samples to gradually narrow the target number and optimize the composition of the diagnostic panel. The diagnostic performance of the obtained panel was evaluated in different clinical scenarios.<h4>Results</h4>A total of 1,627 hypermethylated promoter targets in the BC cell lines was identified by Illumina sequencing. The top 104 hypermethylated targets were reduced to eight genes (VAX1, KCNV1, ECEL1, TMEM26, TAL1, PROX1, SLC6A20, and LMX1A) after the urine DNA screening in a small sample size of 8 normal control and 18 BC subjects. Validation in an independent sample of 212 BC patients enabled the optimization of five methylation targets, including VAX1, KCNV1, TAL1, PPOX1, and CFTR, which was obtained in our previous study, for BC diagnosis with a sensitivity and specificity of 88.68% and 87.25%, respectively. In addition, the methylation of VAX1 and LMX1A was found to be associated with BC recurrence.<h4>Conclusions</h4>We identified a promising diagnostic marker panel for early non-invasive detection and subsequent BC surveillance.Yangxing ZhaoShicheng GuoJinfeng SunZhaohui HuangTongyu ZhuHongyu ZhangJun GuYinghua HeWei WangKelong MaJina WangJian YuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35175 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yangxing Zhao Shicheng Guo Jinfeng Sun Zhaohui Huang Tongyu Zhu Hongyu Zhang Jun Gu Yinghua He Wei Wang Kelong Ma Jina Wang Jian Yu Methylcap-seq reveals novel DNA methylation markers for the diagnosis and recurrence prediction of bladder cancer in a Chinese population.
description	<h4>Purpose</h4>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.<h4>Experimental design</h4>The methyl-DNA binding domain (MBD) capture technique, methylCap/seq, was performed to screen for specific hypermethylated CpG islands in two BC cell lines (5637 and T24). The top one hundred hypermethylated targets were sequentially screened by MSP in urine samples to gradually narrow the target number and optimize the composition of the diagnostic panel. The diagnostic performance of the obtained panel was evaluated in different clinical scenarios.<h4>Results</h4>A total of 1,627 hypermethylated promoter targets in the BC cell lines was identified by Illumina sequencing. The top 104 hypermethylated targets were reduced to eight genes (VAX1, KCNV1, ECEL1, TMEM26, TAL1, PROX1, SLC6A20, and LMX1A) after the urine DNA screening in a small sample size of 8 normal control and 18 BC subjects. Validation in an independent sample of 212 BC patients enabled the optimization of five methylation targets, including VAX1, KCNV1, TAL1, PPOX1, and CFTR, which was obtained in our previous study, for BC diagnosis with a sensitivity and specificity of 88.68% and 87.25%, respectively. In addition, the methylation of VAX1 and LMX1A was found to be associated with BC recurrence.<h4>Conclusions</h4>We identified a promising diagnostic marker panel for early non-invasive detection and subsequent BC surveillance.
format	article
author	Yangxing Zhao Shicheng Guo Jinfeng Sun Zhaohui Huang Tongyu Zhu Hongyu Zhang Jun Gu Yinghua He Wei Wang Kelong Ma Jina Wang Jian Yu
author_facet	Yangxing Zhao Shicheng Guo Jinfeng Sun Zhaohui Huang Tongyu Zhu Hongyu Zhang Jun Gu Yinghua He Wei Wang Kelong Ma Jina Wang Jian Yu
author_sort	Yangxing Zhao
title	Methylcap-seq reveals novel DNA methylation markers for the diagnosis and recurrence prediction of bladder cancer in a Chinese population.
title_short	Methylcap-seq reveals novel DNA methylation markers for the diagnosis and recurrence prediction of bladder cancer in a Chinese population.
title_full	Methylcap-seq reveals novel DNA methylation markers for the diagnosis and recurrence prediction of bladder cancer in a Chinese population.
title_fullStr	Methylcap-seq reveals novel DNA methylation markers for the diagnosis and recurrence prediction of bladder cancer in a Chinese population.
title_full_unstemmed	Methylcap-seq reveals novel DNA methylation markers for the diagnosis and recurrence prediction of bladder cancer in a Chinese population.
title_sort	methylcap-seq reveals novel dna methylation markers for the diagnosis and recurrence prediction of bladder cancer in a chinese population.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/d330ac05113f4386a57323857de25dc5
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Methylcap-seq reveals novel DNA methylation markers for the diagnosis and recurrence prediction of bladder cancer in a Chinese population.

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