医学
DNA甲基化
前瞻性队列研究
甲基化
肿瘤科
膀胱癌
膀胱癌
泌尿科
泌尿系统
癌症
内科学
中心(范畴论)
DNA
妇科
遗传学
基因
基因表达
结晶学
化学
生物
作者
Tetsuya Shindo,Takashi Shimizu,Masanori Nojima,Takeshi Niinuma,Reo Maruyama,Hiroshi Kitajima,Masahiro Kai,Naoki Itoh,Hiromu Suzuki,Naoya Masumori
出处
期刊:Urology
[Elsevier]
日期:2018-03-01
卷期号:113: 71-78
被引量:16
标识
DOI:10.1016/j.urology.2017.11.025
摘要
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 patients with NMIBC 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 end point was detection of intravesical recurrence; the secondary end point was prediction of late recurrence. The number of methylated genes (M-score) 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 <.01). Multivariate analysis revealed that high M-scores were independently associated with current (P = .028) and late recurrence (P = .026). Elevated levels of urinary DNA methylation were also strongly associated with recurrence and radical cystectomy. Conclusion Our data suggest that urinary methylation of miRNA genes may be a useful marker for detecting and predicting BCa recurrence. 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. A series of 207 self-voided urine samples were prospectively collected from 132 patients with NMIBC 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 end point was detection of intravesical recurrence; the secondary end point was prediction of late recurrence. The number of methylated genes (M-score) or quantitative level of methylation were compared with outcomes. 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 <.01). Multivariate analysis revealed that high M-scores were independently associated with current (P = .028) and late recurrence (P = .026). Elevated levels of urinary DNA methylation were also strongly associated with recurrence and radical cystectomy. Our data suggest that urinary methylation of miRNA genes may be a useful marker for detecting and predicting BCa recurrence.
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