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

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DOI

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  • 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
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Background: 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. Results: 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%. Conclusions: 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.

OriginalsprogEngelsk
Artikelnummer115
TidsskriftClinical Epigenetics
Vol/bind14
Udgave nummer1
ISSN1868-7075
DOI
StatusUdgivet - dec. 2022

Bibliografisk note

Funding Information:
We are truly thankful to the patients and healthy individuals that provided urine samples for this study. Moreover, the bioinformatic analyses were performed on the TSD (Tjeneste for Sensitive Data) facilities, owned by the University of Oslo, operated and developed by the TSD service group at the University of Oslo, IT-Department (USIT) (tsd-drift@usit.uio.no) and on resources provided by UNINETT Sigma2—the National Infrastructure for High Performance Computing and Data Storage in Norway.

Funding Information:
This work was supported by a grant from the South-Eastern Norway Regional Health Authority (project number 40093, to GEL), a Cancer-BIOTEK Grant No. (254834), and innovation funding from the South-Eastern Norway Regional Health Authority and the University of Oslo, Norway. The funding sources had no role in this study.

Publisher Copyright:
© 2022, The Author(s).

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