Evaluation of an Epigenetic Profile for the Detection of Bladder Cancer in Patients with Hematuria

The Journal of Urology
Kim E M van KesselWim Van Criekinge

Abstract

Many patients enter the care cycle with gross or microscopic hematuria and undergo cystoscopy to rule out bladder cancer. Sensitivity of this invasive examination is limited, leaving many patients at risk for undetected cancer. To improve current clinical practice more sensitive and noninvasive screening methods should be applied. A total of 154 urine samples were collected from patients with hematuria, including 80 without and 74 with bladder cancer. DNA from cells in the urine was epigenetically profiled using 2 independent assays. Methylation specific polymerase chain reaction was performed on TWIST1. SNaPshot™ methylation analysis was done for different loci of OTX1 and ONECUT2. Additionally all samples were analyzed for mutation status of TERT (telomerase reverse transcriptase), PIK3CA, FGFR3 (fibroblast growth factor receptor 3), HRAS, KRAS and NRAS. The combination of TWIST1, ONECUT2 (2 loci) and OTX1 resulted in the best overall performing panel. Logistic regression analysis on these methylation markers, mutation status of FGFR3, TERT and HRAS, and patient age resulted in an accurate model with 97% sensitivity, 83% specificity and an AUC of 0.93 (95% CI 0.88-0.98). Internal validation led to an optimism corrected AUC of...Continue Reading

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Citations

Aug 10, 2016·Molecular Diagnosis & Therapy·Javier C AnguloSantiago Ropero
Oct 30, 2016·Expert Review of Molecular Diagnostics·Laura-Maria KrabbeYair Lotan
Oct 18, 2016·The Journal of Urology·Kim E M van KesselEllen C Zwarthoff
Feb 7, 2017·Clinical Epigenetics·Andrew FeberJohn D Kelly
May 1, 2018·Expert Review of Molecular Diagnostics·Moritz MaasTilman Todenhöfer
Oct 18, 2018·Current Urology Reports·William Tabayoyong, Ashish M Kamat
Nov 28, 2018·Nature Reviews. Genetics·María Berdasco, Manel Esteller
Mar 12, 2019·Current Opinion in Urology·Abhishek Bhat, Chad R Ritch
Feb 13, 2018·Oncology Letters·Xuebao XiangPengcheng Li
Apr 19, 2018·Nature Reviews. Clinical Oncology·Alexander KochManon van Engeland
Apr 23, 2019·International Journal of Cancer. Journal International Du Cancer·Christina U KöhlerThomas Brüning
Jan 16, 2016·Disease Markers·Hiroki Ide, Hiroshi Miyamoto
Nov 13, 2018·Bladder Cancer·Niranjan J SathianathenBadrinath R Konety
Feb 17, 2019·International Journal of Molecular Sciences·Eline OeyenInge Mertens
Jun 4, 2020·Cancers·Manuel Castanheira de OliveiraRicardo Ribeiro
Dec 26, 2017·Expert Review of Precision Medicine and Drug Development·Mohamad M KronfolJoseph L McClay
Dec 6, 2019·Frontiers in Genetics·Warwick J LockeJason P Ross
Jun 17, 2020·BJU International·Anouk E HentschelJakko A Nieuwenhuijzen
Dec 19, 2020·Biomolecules·Francesca GalardiMatteo Benelli
Feb 27, 2021·Frontiers in Oncology·Yansheng XuHongzhao Li
Mar 31, 2021·Clinical Genitourinary Cancer·Grant M HenningZachary L Smith
Apr 4, 2021·Journal of Personalized Medicine·Matteo FerroDaniela Terracciano

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