ArticleBMC cancer2022
Identification and validation of methylated PENK gene for early detection of bladder cancer using urine DNA.
Article in BMC cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Diagnostic potential of urinaryTranslational andrology and urology · 2026Article
- Methylation biomarkers can distinguish pleural mesothelioma from healthy pleura and other pleural pathologies.Molecular oncology · 2026Article
- EarlyTect BCD Plus: A urine-based dual site PENK methylation test for risk-based cystoscopy triage in haematuria.BJUI compass · 2026Article
- Prognostic model based on stem cells and oxidative stress related genes for ovarian cancer.Medicine · 2026Article
- Review
- Unleashing the potential of urine DNA methylation detection: Advancements in biomarkers, clinical applications, and emerging technologies.Current urology · 2025Article
- Diagnostic accuracy of urinary PENK methylation test for urothelial and other cancers: A prospective study.Scientific reports · 2025Article
- Review
- Clinical Validation of the Proenkephalin (European urology open science · 2024Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundEarly detection of bladder cancer (BCa) offers patients a favorable outcome and avoids the need for cystectomy. Development of an accurate and sensitive noninvasive BCa diagnostic test is imperative. DNA methylation is an early epigenetic event in the development of BCa. Certain specific aberrant methylations could serve as useful biomarkers. The aim of this study was to identify methylation biomarkers for early detection of BCa.
methodsCpG methylation microarray analysis was conducted on primary tumors with varying stages (T1-T4) and paired nontumor tissues from nine BCa patients. Bisulfite-pyrosequencing was performed to confirm the methylation status of candidate genes in tissues and urine sediments (n = 51). Among them, PENK was selected as a potential candidate and validated using an independent set of 169 urine sediments (55 BCa, 25 benign urologic diseases, 8 other urologic cancers, and 81 healthy controls) with a quantitative methylation-specific real time PCR (mePENK-qMSP). All statistical analyses were performed using MedCalc software version 9.3.2.0.
resultsCpG methylation microarray analysis and stepwise validation by bisulfite-pyrosequencing for tissues and urine sediments supported aberrant methylation sites of the PENK gene as potential biomarkers for early detection of BCa. Clinical validation of the mePENK-qMSP test using urine sediment-DNA showed a sensitivity of 86.5% (95% CI: 71.2 - 95.5%), a specificity of 92.5% (95% CI: 85.7 - 96.7%), and an area under ROC of 0.920 (95% CI: 0.863 - 0.959) in detecting Ta high-grade and advanced tumor stages (T1-T4) of BCa patients. Sensitivities for Ta low-grade, Ta high-grade, T1 and T2-T4 were 55.6, 83.3, 88.5, and 100%, respectively. Methylation status of PENK was not correlated with sex, age or stage, while it was associated with the tumor grade of BCa.
conclusionsIn this study, we analyzed the comprehensive patterns of DNA methylation identified that PENK methylation possesses a high potential as a biomarker for urine-based early detection of BCa. Validation of PENK methylation confirms that it could significantly improve the noninvasive detection of BCa.
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