Evaluation of Urinary DNA Methylation as a Marker for Recurrent Bladder Cancer: a Two-Center Prospective Study. - PubMed - NCBI
Urology. 2017 Nov 28. pii: S0090-4295(17)31223-2. doi: 10.1016/j.urology.2017.11.025. [Epub ahead of print]
Evaluation of Urinary DNA Methylation as a Marker for Recurrent Bladder Cancer: a Two-Center Prospective Study.
Abstract
OBJECTIVE:
To clarify the clinical utility of urinary DNA methylation for detection of intravesical recurrence of non-muscle invasive BCa (NMIBC), we performed a 2 center prospective study. PATIENTS AND METHODS:
A series of 207 self-voided urine samples were prospectively collected from 132 NMIBC patients who had undergone transurethral resection of BCa. Methylation of miRNA genes (miR-9-3, miR-124-2, miR-124-3 and miR-137) was analyzed using bisulfite pyrosequencing. The primary endpoint was detection of intravesical recurrence; the secondary endpoint was prediction of late recurrence. The number of methylated genes (M-score) and/or quantitative level of methylation were compared with outcomes. RESULTS:
Twenty six urine specimens were collected on the same day intravesical recurrence was detected, and 14 were collected from patients whose recurrences were found during the subsequent follow-up period (0 - 632 days, mean, 342.2 days). For detection of current recurrence, M-scores achieved 61.5% sensitivity and 74.0% specificity, and the area under the ROC curve was 0.71. Regarding prediction of late recurrence, patients with a high M-score (≥ 3) showed worse recurrence-free survival (P < 0.01). Multivariate analysis revealed that high M-scores were independently associated with current (P = 0.028) and late recurrence (P = 0.026). Elevated levels of urinary DNA methylation were also strongly associated with recurrence and radical cystectomy. CONCLUSIONS:
Our data suggest that urinary methylation of miRNA genes may be a useful marker for detecting and predicting BCa recurrence. Copyright © 2017 Elsevier Inc. All rights reserved.
KEYWORDS:
Intravesical recurrence; Methylation; Urinary biomarker; Urothelial carcinoma
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