Urine cell-based DNA methylation classifier for monitoring bladder cancer

Clinical Epigenetics
Antoine G Van der HeijdenAntonio Alcaraz

Abstract

Current standard methods used to detect and monitor bladder cancer (BC) are invasive or have low sensitivity. This study aimed to develop a urine methylation biomarker classifier for BC monitoring and validate this classifier in patients in follow-up for bladder cancer (PFBC). Voided urine samples (N = 725) from BC patients, controls, and PFBC were prospectively collected in four centers. Finally, 626 urine samples were available for analysis. DNA was extracted from the urinary cells and bisulfite modificated, and methylation status was analyzed using pyrosequencing. Cytology was available from a subset of patients (N = 399). In the discovery phase, seven selected genes from the literature (CDH13, CFTR, NID2, SALL3, TMEFF2, TWIST1, and VIM2) were studied in 111 BC and 57 control samples. This training set was used to develop a gene classifier by logistic regression and was validated in 458 PFBC samples (173 with recurrence). A three-gene methylation classifier containing CFTR, SALL3, and TWIST1 was developed in the training set (AUC 0.874). The classifier achieved an AUC of 0.741 in the validation series. Cytology results were available for 308 samples from the validation set. Cytology achieved AUC 0.696 whereas the classifier ...Continue Reading

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Citations

Jan 17, 2019·Expert Review of Molecular Diagnostics·Claire FranczakAlexandre Harlé
Feb 6, 2020·International Journal of Molecular Sciences·João LoboRui Henrique
Dec 5, 2019·Expert Review of Molecular Diagnostics·Antonio Lopez-BeltranRodolfo Montironi
Jul 10, 2019·Experimental and Therapeutic Medicine·Ka WangShiyuan Xu
Oct 23, 2019·World Journal of Gastroenterology : WJG·Kyle J AndersonPatricia M Scott
Dec 19, 2019·Frontiers in Genetics·Victor G MartinezJesus Maria Paramio
Feb 13, 2020·International Journal of Molecular Sciences·Michael RoseEdgar Dahl
Sep 25, 2018·Frontiers in Oncology·Giorgio SantoniNicola Battelli
Feb 15, 2020·Investigative and Clinical Urology·Jayoung KimWun-Jae Kim
Jul 10, 2020·Molecular and Cellular Pediatrics·Shivanthan ShanthikumarRichard Saffery
Apr 25, 2020·International Journal of Molecular Sciences·Patricia ScottRobert Cormier
Jul 14, 2020·Current Genomics·Amit SharmaJörg Ellinger
Aug 21, 2020·The Journal of Clinical Investigation·Xu ChenTianxin Lin

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Methods Mentioned

BETA
PCR
Assay

Software Mentioned

pROC R - package
PyroQ CpG
PyroMark Assay Design

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