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Validation of a DNA...
Validation of a DNA Methylation-Mutation Urine Assay to Select Patients with Hematuria for Cystoscopy
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- van Kessel, Kim E. M. (författare)
- Erasmus MC, Dept Pathol, Rotterdam, Netherlands.
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- Beukers, Willemien (författare)
- Erasmus MC, Dept Pathol, Rotterdam, Netherlands.
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- Lurkin, Irene (författare)
- Erasmus MC, Dept Pathol, Rotterdam, Netherlands.
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- Ziel-van der Made, Angelique (författare)
- Erasmus MC, Dept Pathol, Rotterdam, Netherlands.
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- van der Keur, Kirstin A. (författare)
- Erasmus MC, Dept Pathol, Rotterdam, Netherlands.
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- Boormans, Joost L. (författare)
- Erasmus MC, Dept Urol, Rotterdam, Netherlands.
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- Dyrskjot, Lars (författare)
- Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark.
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- Marquez, Mirari (författare)
- Spanish Natl Canc Res Ctr, Genet & Mol Epidemiol Grp, Madrid, Spain.
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- Orntoft, Torben F. (författare)
- Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark.
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- Real, Francisco X. (författare)
- Spanish Natl Canc Res Ctr, Epithelial Carcinogenesis Grp, Madrid, Spain.;Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona, Spain.
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- Segersten, Ulrika (författare)
- Uppsala universitet,Urologkirurgi
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- Malats, Nuria (författare)
- Spanish Natl Canc Res Ctr, Genet & Mol Epidemiol Grp, Madrid, Spain.
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- Malmström, Per-Uno (författare)
- Uppsala universitet,Urologkirurgi
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- Van Criekinge, Wim (författare)
- MDxHealth Inc, Irvine, CA USA.;Univ Ghent, Lab Bioinformat & Computat Genom, Ghent, Belgium.
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- Zwarthoff, Ellen C. (författare)
- Erasmus MC, Dept Pathol, Rotterdam, Netherlands.
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Erasmus MC, Dept Pathol, Rotterdam, Netherlands Erasmus MC, Dept Urol, Rotterdam, Netherlands. (creator_code:org_t)
- Ovid Technologies (Wolters Kluwer Health), 2017
- 2017
- Engelska.
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 197:3, s. 590-595
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Purpose: Only 3% to 28% of patients referred to the urology clinic for hematuria are diagnosed with bladder cancer. Cystoscopy leads to high diagnostic costs and a high patient burden. Therefore, to improve the selection of patients for cystoscopy and reduce costs and over testing we aimed to validate a recently developed diagnostic urine assay.Materials and Methods: Included in study were 200 patients from a total of 3 European countries who underwent cystoscopy for hematuria, including 97 with bladder cancer and 103 with nonmalignant findings. Voided urine samples were collected prior to cystoscopy. DNA was extracted and analyzed for mutations in FGFR3, TERT and HRAS, and methylation of OTX1, ONECUT2 and TWIST1. Logistic regression was used to analyze the association between predictor variables and bladder cancer.Results: Combining the methylation and mutation markers with age led to an AUC of 0.96 (95% CI 0.92e0.99) with 93% sensitivity and 86% specificity, and an optimism corrected AUC of 0.95. The AUC was higher for T1 or greater tumors compared to Ta tumors (0.99 vs 0.93). The AUC was also higher for high grade tumors compared to low grade tumors (1.00 vs 0.93). Overall negative predictive value was 99% based on the 5% to 10% prevalence of bladder cancer in patients with hematuria. This would lead to a 77% reduction in diagnostic cystoscopy.Conclusions: Analyzing hematuria patients for the risk of bladder cancer using novel molecular markers may lead to a reduction in diagnostic cystoscopy. Combining methylation analysis (OTX1, ONECUT2 and TWIST1) with mutation analysis (FGFR3, TERT and HRAS) and patient age resulted in a validated accurate prediction model.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
Nyckelord
- urinary bladder neoplasms
- hematuria
- biomarkers
- tumor
- urinalysis
- methylation
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- art (ämneskategori)
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Beukers, Willemi ...
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Lurkin, Irene
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Ziel-van der Mad ...
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Dyrskjot, Lars
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Segersten, Ulrik ...
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