Detection of colorectal cancer in urine using DNA methylation analysis

Abstract Colorectal cancer (CRC) is the second leading cause for cancer-related death globally. Clinically, there is an urgent need for non-invasive CRC detection. This study assessed the feasibility of CRC detection by analysis of tumor-derived methylated DNA fragments in urine. Urine samples, incl...

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Autores principales:	S. Bach, I. Paulis, N. R. Sluiter, M. Tibbesma, I. Martin, M. A. van de Wiel, J. B. Tuynman, I. Bahce, G. Kazemier, R. D. M. Steenbergen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1b71f26446b74fb78e114a936d66f822
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spelling	oai:doaj.org-article:1b71f26446b74fb78e114a936d66f8222021-12-02T14:16:42ZDetection of colorectal cancer in urine using DNA methylation analysis10.1038/s41598-021-81900-62045-2322https://doaj.org/article/1b71f26446b74fb78e114a936d66f8222021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81900-6https://doaj.org/toc/2045-2322Abstract Colorectal cancer (CRC) is the second leading cause for cancer-related death globally. Clinically, there is an urgent need for non-invasive CRC detection. This study assessed the feasibility of CRC detection by analysis of tumor-derived methylated DNA fragments in urine. Urine samples, including both unfractioned and supernatant urine fractions, of 92 CRC patients and 63 healthy volunteers were analyzed for DNA methylation levels of 6 CRC-associated markers (SEPT9, TMEFF2, SDC2, NDRG4, VIM and ALX4). Optimal marker panels were determined by two statistical approaches. Methylation levels of SEPT9 were significantly increased in urine supernatant of CRC patients compared to controls (p < 0.0001). Methylation analysis in unfractioned urine appeared inaccurate. Following multivariate logistic regression and classification and regression tree analysis, a marker panel consisting of SEPT9 and SDC2 was able to detect up to 70% of CRC cases in urine supernatant at 86% specificity. First evidence is provided for CRC detection in urine by SEPT9 methylation analysis, which combined with SDC2 allows for an optimal differentiation between CRC patients and controls. Urine therefore provides a promising liquid biopsy for non-invasive CRC detection.S. BachI. PaulisN. R. SluiterM. TibbesmaI. MartinM. A. van de WielJ. B. TuynmanI. BahceG. KazemierR. D. M. SteenbergenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q S. Bach I. Paulis N. R. Sluiter M. Tibbesma I. Martin M. A. van de Wiel J. B. Tuynman I. Bahce G. Kazemier R. D. M. Steenbergen Detection of colorectal cancer in urine using DNA methylation analysis
description	Abstract Colorectal cancer (CRC) is the second leading cause for cancer-related death globally. Clinically, there is an urgent need for non-invasive CRC detection. This study assessed the feasibility of CRC detection by analysis of tumor-derived methylated DNA fragments in urine. Urine samples, including both unfractioned and supernatant urine fractions, of 92 CRC patients and 63 healthy volunteers were analyzed for DNA methylation levels of 6 CRC-associated markers (SEPT9, TMEFF2, SDC2, NDRG4, VIM and ALX4). Optimal marker panels were determined by two statistical approaches. Methylation levels of SEPT9 were significantly increased in urine supernatant of CRC patients compared to controls (p < 0.0001). Methylation analysis in unfractioned urine appeared inaccurate. Following multivariate logistic regression and classification and regression tree analysis, a marker panel consisting of SEPT9 and SDC2 was able to detect up to 70% of CRC cases in urine supernatant at 86% specificity. First evidence is provided for CRC detection in urine by SEPT9 methylation analysis, which combined with SDC2 allows for an optimal differentiation between CRC patients and controls. Urine therefore provides a promising liquid biopsy for non-invasive CRC detection.
format	article
author	S. Bach I. Paulis N. R. Sluiter M. Tibbesma I. Martin M. A. van de Wiel J. B. Tuynman I. Bahce G. Kazemier R. D. M. Steenbergen
author_facet	S. Bach I. Paulis N. R. Sluiter M. Tibbesma I. Martin M. A. van de Wiel J. B. Tuynman I. Bahce G. Kazemier R. D. M. Steenbergen
author_sort	S. Bach
title	Detection of colorectal cancer in urine using DNA methylation analysis
title_short	Detection of colorectal cancer in urine using DNA methylation analysis
title_full	Detection of colorectal cancer in urine using DNA methylation analysis
title_fullStr	Detection of colorectal cancer in urine using DNA methylation analysis
title_full_unstemmed	Detection of colorectal cancer in urine using DNA methylation analysis
title_sort	detection of colorectal cancer in urine using dna methylation analysis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1b71f26446b74fb78e114a936d66f822
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Detection of colorectal cancer in urine using DNA methylation analysis

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