Journal
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
Volume 36, Issue 7, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.urolonc.2018.04.001
Keywords
DNA methylation; Noninvasive detection; Transitional cell carcinoma; Urinary biomarkers; Urothelial carcinoma
Categories
Funding
- Collaborative Research Foundation of Peking University Health Science Center
- National Taiwan University, College of Medicine [BMU20120318]
- Natural Science Foundation of Beijing Municipality [7152146]
- Clinical Features Research of Capital [Z151100004015173]
- Capital Health Research and Development Special Fund [2016-1-4077]
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Introduction: Hematuria is the most common symptom of urothelial carcinomas (UC) but is often idiopathic. Cystoscopy is expensive which involves considerable patient discomfort, and conventional urine cytology for noninvasive UC detection and disease monitoring suffers from poor sensitivity. We aim to evaluate the performance of genes selected from a previous study in detecting UC, especially among patients with gross hematuria, as well as upper tract urothelial carcinoma (UTUC) and bladder carcinoma separately, in voided urine samples. Methods: Using methylation-specific polymerise chain reaction, we examined the promoter methylation status of 10 genes in voided urine samples among 473 patients at our institution, including 217 UC patients and 256 control subjects. Results: The final combination of VIM, CDH1, SALL3, TMEFF2, RASSF1A, BRCA1, GDF15, and ABCC6 identified UC with a sensitivity of 0.83 and a specificity of 0.60. Additionally, a panel of selected genes (CDH1, HSPA2, RASSF1A, TMEFF2, VIM, and GDF15) identified UTUC with a sensitivity of 0.82 and a specificity of 0.68, while a panel of selected genes (VIM, RASSF1A, GDF15, and TMEFF2) identified bladder carcinoma with a sensitivity of 0.82 and a specificity of 0.53. Remarkably, a different panel (CDH1, SALL3, THBS1, TMEFF2, VIM, and GDF15) identified UC in patients with gross hematuria with 0.89 sensitivity and 0.74 specificity, and sensitivity (0.91) and specificity (0.92) could be achieved when cytology was included. Conclusions: The selected urine-DNA methylation biomarkers are reliable, noninvasive, and cost-effective diagnostic tools for bladder carcinoma and UTUC, especially among patients with gross hematuria. (C) 2018 Published by Elsevier Inc.
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