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

Clin Epigenetics. 2022 Sep 17;14(1):115. doi: 10.1186/s13148-022-01335-2.

Abstract

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.

Keywords: Biomarkers; Bladder cancer; Cystoscopy; DNA methylation; Detection; Digital PCR; Hematuria; Methylome sequencing; Non-invasive detection; Urine test.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / urine
  • DNA Methylation
  • Hematuria / diagnosis
  • Hematuria / genetics
  • Humans
  • Prospective Studies
  • Urinary Bladder Neoplasms* / diagnosis
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / urine

Substances

  • Biomarkers, Tumor