Dataset Information

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

ABSTRACT:

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 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.

Results

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.

Conclusions

We identified a promising diagnostic marker panel for early non-invasive detection and subsequent BC surveillance.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC3328468 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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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

<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 Cp ...[more]

PMID: 22529986

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Project description:BackgroundCurrently, the clinical strategy for diagnosis of non-muscle invasive bladder cancer (NMIBC) such as cystoscopy and cytology are invasive and/or with limited accuracy. OncoUrine, a urinary assay for mutation and methylation biomarkers, have showed a high accuracy in the detection of upper tract urinary carcinoma (UTUC) patients with hematuria. The aim of this study is to evaluate the performance of OncoUrine in diagnosis of NMIBC patients.MethodsIn this multicenter prospective study, a total of 203 patients were enrolled, including 60 patients present with hematuria and 143 NMIBC patients under recurrence surveillance. Urine samples were collected before cystoscopy to undergo OncoUrine test. OncoUrine performance was calculated compared to clinical standard methods in hematuria cohort and recurrence surveillance cohort, respectively. Furthermore, NMIBC patients were followed up with a median time of 20.5 months (range 0.03 to 24.03 months) to assess the predictive value of OncoUrine during recurrence monitoring.ResultsFor bladder cancer diagnosis, OncoUrine tested 47 samples and achieved a sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) of 80% (95% CI 44.2-96.5)/91.9% (95% CI 77.0-97.9)/72.7% (95% CI 39.3-92.7)/94.4% (95% CI 80.0-99.0) (kappa value 69.4%, 95% CI 44.4-94.3), indicating 72.3% of unnecessary cystoscopy. For recurrence diagnosis, OncoUrine tested 93 samples, and the sensitivity/specificity/PPV/NPV was 100% (95% CI 59.8-100.0)/68.2% (95% CI 57.1-77.7)/22.9% (95% CI 11.0-40.6)/100% (95% CI 92.3-100.0) (kappa value 27.0%, 95% CI 11.1-42.8), indicating 62.4% of spared cystoscopy. What is more, OncoUrine correctly predicted 80% (20/25) of final recurrence with 12/25 (48%) patients who were OncoUrine positive, but cystoscopy negative was followed with recurrence during follow-up. The test result of OncoUrine was also found significantly correlated with recurrence free survival (RFS) of NMIBC patients (median 34.4-month vs unreached; HR 6.0, 95% CI 2.7-13.5, P < 0.0001).ConclusionsOncoUrine showed potential value to reduce the frequency of unnecessary cystoscopy and the healthcare cost of bladder cancer patients. Patients with positive test results represented a population who were at high risk of recurrence and thus should be subject to frequent surveillance to ensure timely detection of any potential recurrence. This study has been registered in ClinicalTrials.gov with the number NCT04994197 posted on August 2021.

Dataset Information

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

Purpose

Experimental design

Results

Conclusions

Publications

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

Similar Datasets

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