Cystoscopy is the gold standard for bladder cancer detection, but is costly, invasive and has imperfect diagnostic accuracy. We aimed to identify novel and accurate DNA methylation biomarkers for non-invasive detection of bladder cancer in urine, with the potential to reduce the number of cystoscopies among hematuria patients.
Biomarker candidates (n = 32) were identified from methylome sequencing of urological cancer cell lines (n = 16) and subjected to targeted methylation analysis in tissue samples (n = 60). The most promising biomarkers (n = 8) were combined into a panel named BladMetrix. The performance of BladMetrix in urine was assessed in a discovery series (n = 112), consisting of bladder cancer patients, patients with other urological cancers and healthy individuals, resulting in 95.7% sensitivity and 94.7% specificity. BladMetrix was furthermore evaluated in an independent prospective and blinded series of urine from patients with gross hematuria (n = 273), achieving 92.1% sensitivity, 93.3% specificity and a negative predictive value of 98.1%, with the potential to reduce the number of cystoscopies by 56.4%.
We here present BladMetrix, a novel DNA methylation urine test for non-invasive detection of bladder cancer, with high accuracy across tumor grades and stages, and the ability to spare a significant number of cystoscopies among patients with gross hematuria.
Clinical epigenetics. 2022 Sep 17*** epublish ***
Heidi Dietrichson Pharo, Marine Jeanmougin, Eirill Ager-Wick, Hege Marie Vedeld, Anne Klara Sørbø, Christina Dahl, Louise Katrine Larsen, Hilde Honne, Sara Brandt-Winge, May-Britt Five, Sara Monteiro-Reis, Rui Henrique, Carmen Jeronimo, Kenneth Steven, Rolf Wahlqvist, Per Guldberg, Guro Elisabeth Lind
Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway., Department of Urology, Oslo University Hospital, Oslo, Norway., Danish Cancer Society Research Center, 2100, Copenhagen, Denmark., Cancer Biology and Epigenetics Group, Research Center (CI-IPOP), Portoguese Oncology Institute of Porto (IPO Porto), Porto, Portugal., Department of Urology, University of Copenhagen, Herlev Hospital, Herlev, Denmark., Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway. .