Abstract
DNA methylation analysis of full void urine and urine pellet seems promising for bladder cancer (BC) detection and surveillance. Urinary cell-free DNA from urine supernatant is now gaining interest for other molecular tests in BC. This study aims to evaluate which urine fraction is preferred for BC diagnosis using methylation markers: full void urine, urine pellet or supernatant. Methylation levels of nine markers were determined in the three urine fractions and correlated with their respective tumor tissues in BC patients and compared to controls. For all markers and marker panel GHSR/MAL, diagnostic performance was determined by calculating the area under the curve (AUC) of the respective receiver operating characteristic curves. For most of the markers, there was a significant correlation between the methylation levels in each of the urine fractions and the matched tumor tissues. Urine pellet was the most representative fraction. Generally, AUCs for BC diagnosis were comparable among the fractions. The highest AUC was obtained for GHSR/MAL in urine pellet: AUC 0.87 (95% confidence interval: 0.73–1.00), corresponding to a sensitivity of 78.6% and a specificity of 91.7%. Our results demonstrate that cellular and cell-free DNA in urine can be used for BC diagnosis by urinary methylation analysis. Based on our comparative analysis and for practical reasons, we recommend the use of urine pellet.
Highlights
Hematuria is often the first sign of disease in bladder cancer (BC) patients
We showed that full void urine, comprising both cellular and cell-free DNA, can be used for DNA methylation analysis in BC patients
We examined the correlation between the methylation levels of the nine markers between each of the three urine fractions and the matched bladder tumor tissues in 14 BC patients
Summary
Hematuria is often the first sign of disease in bladder cancer (BC) patients. At referral, an endoscopic inspection of the bladder wall through cystoscopy and imaging of the upper urinary tract is performed.In case BC is diagnosed, regular follow-up cystoscopies are required for multiple years, since disease often recurs or progresses [1]. Hematuria is often the first sign of disease in bladder cancer (BC) patients. An endoscopic inspection of the bladder wall through cystoscopy and imaging of the upper urinary tract is performed. In case BC is diagnosed, regular follow-up cystoscopies are required for multiple years, since disease often recurs or progresses [1]. Biomarker analysis in urine, such as DNA hypermethylation, may be an alternative and effective approach for BC detection and surveillance. Cancers 2020, 12, 859 refers to the addition of a methyl group to cytosine residues in CpG dinucleotides. Many potential urinary methylation markers for BC detection have been investigated, with great variety in diagnostic performance [3,4,5]
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