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Pharo, Heidi Dietrichson; Jeanmougin, Marine; Ager-Wick, Eirill; Vedeld, Hege Marie; Sørbø, Anne Klara; Dahl, Christina; Larsen, Louise Katrine; Honne, Hilde; Brandt-Winge, Sara; Five, May-Britt; Monteiro-Reis, Sara; Henrique, Rui; Jeronimo, Carmen; Steven, Kenneth; Wahlqvist, Rolf; Guldberg, Per; Lind, Guro Elisabeth

BladMetrix: a novel urine DNA methylation test with high accuracy for detection of bladder cancer in hematuria patients

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  • Medientyp: E-Artikel
  • Titel: BladMetrix: a novel urine DNA methylation test with high accuracy for detection of bladder cancer in hematuria patients
  • Beteiligte: Pharo, Heidi Dietrichson; Jeanmougin, Marine; Ager-Wick, Eirill; Vedeld, Hege Marie; Sørbø, Anne Klara; Dahl, Christina; Larsen, Louise Katrine; Honne, Hilde; Brandt-Winge, Sara; Five, May-Britt; Monteiro-Reis, Sara; Henrique, Rui; Jeronimo, Carmen; Steven, Kenneth; Wahlqvist, Rolf; Guldberg, Per; Lind, Guro Elisabeth
  • Erschienen: Springer Science and Business Media LLC, 2022
  • Erschienen in: Clinical Epigenetics
  • Sprache: Englisch
  • DOI: 10.1186/s13148-022-01335-2
  • ISSN: 1868-7075; 1868-7083
  • Schlagwörter: Genetics (clinical) ; Developmental Biology ; Genetics ; Molecular Biology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Biomarker candidates (<jats:italic>n</jats:italic> = 32) were identified from methylome sequencing of urological cancer cell lines (<jats:italic>n</jats:italic> = 16) and subjected to targeted methylation analysis in tissue samples (<jats:italic>n</jats:italic> = 60). The most promising biomarkers (<jats:italic>n</jats:italic> = 8) were combined into a panel named BladMetrix. The performance of BladMetrix in urine was assessed in a discovery series (<jats:italic>n</jats:italic> = 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 (<jats:italic>n</jats:italic> = 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%.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> </jats:sec>
  • Zugangsstatus: Freier Zugang