The use of molecular analyses in voided urine for the assessment of patients with hematuria.

<h4>Introduction</h4>Patients presenting with painless hematuria form a large part of the urological patient population. In many cases, especially in younger patients, the cause of hematuria is harmless. Nonetheless, hematuria could be a symptom of malignant disease and hence most patien...

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Autores principales:	Willemien Beukers, Raju Kandimalla, Diandra van Houwelingen, Hrvoje Kovacic, Jie-Fen D Chin, Hester F Lingsma, Lars Dyrskjot, Ellen C Zwarthoff
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/da2a3a4ea5b4429da57b180a99250969
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spelling	oai:doaj.org-article:da2a3a4ea5b4429da57b180a992509692021-11-18T08:50:56ZThe use of molecular analyses in voided urine for the assessment of patients with hematuria.1932-620310.1371/journal.pone.0077657https://doaj.org/article/da2a3a4ea5b4429da57b180a992509692013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24143252/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Introduction</h4>Patients presenting with painless hematuria form a large part of the urological patient population. In many cases, especially in younger patients, the cause of hematuria is harmless. Nonetheless, hematuria could be a symptom of malignant disease and hence most patients will be subject to cystoscopy. In this study, we aimed to develop a prediction model based on methylation markers in combination with clinical variables, in order to stratify patients with high risk for bladder cancer.<h4>Material and methods</h4>Patients (n=169) presenting with painless hematuria were included. 54 patients were diagnosed with bladder cancer. In the remaining 115 patients, the cause of hematuria was non-malignant. Urine samples were collected prior to cystoscopy. Urine DNA was analyzed for methylation of OSR1, SIM2, OTX1, MEIS1 and ONECUT2. Methylation percentages were calculated and were combined with clinical variables into a logistic regression model.<h4>Results</h4>Logistic regression analysis based on the five methylation markers, age, gender and type of hematuria resulted in an area under the curve (AUC) of 0.88 and an optimism corrected AUC of 0.84 after internal validation by bootstrapping. Using a cut-off value of 0.307 allowed stratification of patients in a low-risk and high-risk group, resulting in a sensitivity of 82% (44/54) and a specificity of 82% (94/115). Most aggressive tumors were found in patients in the high-risk group. The addition of cytology to the prediction model, improved the AUC from 0.88 to 0.89, with a sensitivity and specificity of 85% (39/46) and 87% (80/92), retrospectively.<h4>Conclusions</h4>This newly developed prediction model could be a helpful tool in risk stratification of patients presenting with painless hematuria. Accurate risk prediction might result in less extensive examination of low risk patients and thereby, reducing patient burden and costs. Further validation in a large prospective patient cohort is necessary to prove the true clinical value of this model.Willemien BeukersRaju KandimallaDiandra van HouwelingenHrvoje KovacicJie-Fen D ChinHester F LingsmaLars DyrskjotEllen C ZwarthoffPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e77657 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Willemien Beukers Raju Kandimalla Diandra van Houwelingen Hrvoje Kovacic Jie-Fen D Chin Hester F Lingsma Lars Dyrskjot Ellen C Zwarthoff The use of molecular analyses in voided urine for the assessment of patients with hematuria.
description	<h4>Introduction</h4>Patients presenting with painless hematuria form a large part of the urological patient population. In many cases, especially in younger patients, the cause of hematuria is harmless. Nonetheless, hematuria could be a symptom of malignant disease and hence most patients will be subject to cystoscopy. In this study, we aimed to develop a prediction model based on methylation markers in combination with clinical variables, in order to stratify patients with high risk for bladder cancer.<h4>Material and methods</h4>Patients (n=169) presenting with painless hematuria were included. 54 patients were diagnosed with bladder cancer. In the remaining 115 patients, the cause of hematuria was non-malignant. Urine samples were collected prior to cystoscopy. Urine DNA was analyzed for methylation of OSR1, SIM2, OTX1, MEIS1 and ONECUT2. Methylation percentages were calculated and were combined with clinical variables into a logistic regression model.<h4>Results</h4>Logistic regression analysis based on the five methylation markers, age, gender and type of hematuria resulted in an area under the curve (AUC) of 0.88 and an optimism corrected AUC of 0.84 after internal validation by bootstrapping. Using a cut-off value of 0.307 allowed stratification of patients in a low-risk and high-risk group, resulting in a sensitivity of 82% (44/54) and a specificity of 82% (94/115). Most aggressive tumors were found in patients in the high-risk group. The addition of cytology to the prediction model, improved the AUC from 0.88 to 0.89, with a sensitivity and specificity of 85% (39/46) and 87% (80/92), retrospectively.<h4>Conclusions</h4>This newly developed prediction model could be a helpful tool in risk stratification of patients presenting with painless hematuria. Accurate risk prediction might result in less extensive examination of low risk patients and thereby, reducing patient burden and costs. Further validation in a large prospective patient cohort is necessary to prove the true clinical value of this model.
format	article
author	Willemien Beukers Raju Kandimalla Diandra van Houwelingen Hrvoje Kovacic Jie-Fen D Chin Hester F Lingsma Lars Dyrskjot Ellen C Zwarthoff
author_facet	Willemien Beukers Raju Kandimalla Diandra van Houwelingen Hrvoje Kovacic Jie-Fen D Chin Hester F Lingsma Lars Dyrskjot Ellen C Zwarthoff
author_sort	Willemien Beukers
title	The use of molecular analyses in voided urine for the assessment of patients with hematuria.
title_short	The use of molecular analyses in voided urine for the assessment of patients with hematuria.
title_full	The use of molecular analyses in voided urine for the assessment of patients with hematuria.
title_fullStr	The use of molecular analyses in voided urine for the assessment of patients with hematuria.
title_full_unstemmed	The use of molecular analyses in voided urine for the assessment of patients with hematuria.
title_sort	use of molecular analyses in voided urine for the assessment of patients with hematuria.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/da2a3a4ea5b4429da57b180a99250969
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The use of molecular analyses in voided urine for the assessment of patients with hematuria.

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