Universität zu Köln

Rose, Michael, Bringezu, Sarah, Godfrey, Laura, Fiedler, David, Gaisa, Nadine T., Koch, Maximilian, Bach, Christian, Fuessel, Susanne, Herr, Alexander, Huebner, Doreen, Ellinger, Joerg, Pfister, David, Knuechel, Ruth, Wirth, Manfred P., Boehme, Manja and Dahl, Edgar (2020). ITIH5 and ECRG4 DNA Methylation Biomarker Test (EI-BLA) for Urine-Based Non-Invasive Detection of Bladder Cancer. Int. J. Mol. Sci., 21 (3). BASEL: MDPI. ISSN 1422-0067

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Abstract

Bladder cancer is one of the more common malignancies in humans and the most expensive tumor for treating in the Unites States (US) and Europe due to the need for lifelong surveillance. Non-invasive tests approved by the FDA have not been widely adopted in routine diagnosis so far. Therefore, we aimed to characterize the two putative tumor suppressor genes ECRG4 and ITIH5 as novel urinary DNA methylation biomarkers that are suitable for non-invasive detection of bladder cancer. While assessing the analytical performance, a spiking experiment was performed by determining the limit of RT112 tumor cell detection (range: 100-10,000 cells) in the urine of healthy donors in dependency of the processing protocols of the RWTH cBMB. Clinically, urine sediments of 474 patients were analyzed by using quantitative methylation-specific PCR (qMSP) and Methylation Sensitive Restriction Enzyme (MSRE) qPCR techniques. Overall, ECRG4-ITIH5 showed a sensitivity of 64% to 70% with a specificity ranging between 80% and 92%, i.e., discriminating healthy, benign lesions, and/or inflammatory diseases from bladder tumors. When comparing single biomarkers, ECRG4 achieved a sensitivity of 73%, which was increased by combination with the known biomarker candidate NID2 up to 76% at a specificity of 97%. Hence, ITIH5 and, in particular, ECRG4 might be promising candidates for further optimizing current bladder cancer biomarker panels and platforms.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rose, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Bringezu, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Godfrey, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Fiedler, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaisa, Nadine T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Bach, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuessel, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Herr, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Huebner, Doreen UNSPECIFIED UNSPECIFIED UNSPECIFIED Ellinger, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfister, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Knuechel, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirth, Manfred P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boehme, Manja UNSPECIFIED UNSPECIFIED UNSPECIFIED Dahl, Edgar UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-345948
DOI:	10.3390/ijms21031117
Journal or Publication Title:	Int. J. Mol. Sci.
Volume:	21
Number:	3
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1422-0067
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TUMOR-SUPPRESSOR GENE; GROWTH IN-VITRO; EPIGENETIC INACTIVATION; ESOPHAGEAL CANCER; BREAST-CANCER; EXPRESSION; PROGRESSION; METASTASIS; CYTOLOGY; ASSAY Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34594