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

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

doi:10.1186/s13148-022-01335-2

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

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^*

^*Kontaktforfatter

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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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.

Originalsprog	Engelsk
Artikelnummer	115
Tidsskrift	Clinical Epigenetics
Vol/bind	14
Udgave nummer	1
Antal sider	9
ISSN	1868-7083
DOI	https://doi.org/10.1186/s13148-022-01335-2
Status	Udgivet - 17. sep. 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) ([email protected]) 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).

Finansiering

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) ([email protected]) and on resources provided by UNINETT Sigma2—the National Infrastructure for High Performance Computing and Data Storage in Norway. 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.

Dokumenter og links

10.1186/s13148-022-01335-2Licens: CC BY

Open Access VersionForlagets udgivne version, 1,55 MBLicens: CC BY

SDU link

Tjek adgangen til materialet i Syddansk Universitetsbiblioteks søgemaskine

Citationsformater

Pharo, H. D., Jeanmougin, M., Ager-Wick, E., Vedeld, H. M., Sørbø, A. K., Dahl, C., Larsen, L. K., Honne, H., Brandt-Winge, S., Five, M. B., Monteiro-Reis, S., Henrique, R., Jeronimo, C., Steven, K., Wahlqvist, R., Guldberg, P., & Lind, G. E. (2022). BladMetrix: a novel urine DNA methylation test with high accuracy for detection of bladder cancer in hematuria patients. Clinical Epigenetics, 14(1), Artikel 115. https://doi.org/10.1186/s13148-022-01335-2

@article{84d84512562c4638ba310544e182ca12,

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

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, Detection, Digital PCR, DNA methylation, Hematuria, Methylome sequencing, Non-invasive detection, Urine test",

author = "Pharo, \{Heidi Dietrichson\} and Marine Jeanmougin and Eirill Ager-Wick and Vedeld, \{Hege Marie\} and S{\o}rb{\o}, \{Anne Klara\} and Christina Dahl and Larsen, \{Louise Katrine\} and Hilde Honne and Sara Brandt-Winge and Five, \{May Britt\} and Sara Monteiro-Reis and Rui Henrique and Carmen Jeronimo and Kenneth Steven and Rolf Wahlqvist and Per Guldberg and Lind, \{Guro Elisabeth\}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = sep,

day = "17",

doi = "10.1186/s13148-022-01335-2",

language = "English",

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journal = "Clinical Epigenetics",

issn = "1868-7083",

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Pharo, HD, Jeanmougin, M, Ager-Wick, E, Vedeld, HM, Sørbø, AK, Dahl, C, Larsen, LK, Honne, H, Brandt-Winge, S, Five, MB, Monteiro-Reis, S, Henrique, R, Jeronimo, C, Steven, K, Wahlqvist, R, Guldberg, P & Lind, GE 2022, 'BladMetrix: a novel urine DNA methylation test with high accuracy for detection of bladder cancer in hematuria patients', Clinical Epigenetics, bind 14, nr. 1, 115. https://doi.org/10.1186/s13148-022-01335-2

TY - JOUR

T1 - BladMetrix

T2 - a novel urine DNA methylation test with high accuracy for detection of bladder cancer in hematuria patients

AU - Pharo, Heidi Dietrichson

AU - Jeanmougin, Marine

AU - Ager-Wick, Eirill

AU - Vedeld, Hege Marie

AU - Sørbø, Anne Klara

AU - Dahl, Christina

AU - Larsen, Louise Katrine

AU - Honne, Hilde

AU - Brandt-Winge, Sara

AU - Five, May Britt

AU - Monteiro-Reis, Sara

AU - Henrique, Rui

AU - Jeronimo, Carmen

AU - Steven, Kenneth

AU - Wahlqvist, Rolf

AU - Guldberg, Per

AU - Lind, Guro Elisabeth

PY - 2022/9/17

Y1 - 2022/9/17

N2 - 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.

AB - 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.

KW - Biomarkers

KW - Bladder cancer

KW - Cystoscopy

KW - Detection

KW - Digital PCR

KW - DNA methylation

KW - Hematuria

KW - Methylome sequencing

KW - Non-invasive detection

KW - Urine test

U2 - 10.1186/s13148-022-01335-2

DO - 10.1186/s13148-022-01335-2

M3 - Journal article

C2 - 36115961

AN - SCOPUS:85138132295

SN - 1868-7083

VL - 14

JO - Clinical Epigenetics

JF - Clinical Epigenetics

IS - 1

M1 - 115

ER -

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

Abstract

Bibliografisk note

Finansiering

Dokumenter og links

SDU link

Fingeraftryk

Citationsformater