TY - JOUR
T1 - DNA methylation testing for endometrial cancer detection in urine, cervicovaginal self-samples and cervical scrapes
AU - Wever, Birgit M. M.
AU - van den Helder, Rianne
AU - van Splunter, Annina P.
AU - van Gent, Mignon D. J. M.
AU - Kasius, Jenneke C.
AU - Trum, Johannes W.
AU - Verhoeve, Harold R.
AU - van Baal, Wilhelmina M.
AU - Hulbert, Alicia
AU - Verhoef, Lisanne
AU - Heideman, Daniëlle A. M.
AU - Lissenberg-Witte, Birgit I.
AU - van Trommel, Nienke E.
AU - Steenbergen, Renske D. M.
AU - Bleeker, Maaike C. G.
N1 - Funding Information: This research was in part funded by the Hanarth Foundation and Weijerhorst Foundation. The funders had no role in the design of the study; in the collection, analysis or interpretation of data; in the writing of the article; or in the decision to publish the results. Funding Information: The authors would like to thank the URIC biobank team. The authors also thank Danique Wajon for technical assistance. Publisher Copyright: © 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
PY - 2023/7/15
Y1 - 2023/7/15
N2 - Endometrial cancer incidence is rising and current diagnostics often require invasive biopsy procedures. DNA methylation marker analysis of minimally- and non-invasive sample types could provide an easy-to-apply and patient-friendly alternative to determine cancer risk. Here, we compared the performance of DNA methylation markers to detect endometrial cancer in urine, cervicovaginal self-samples and clinician-taken cervical scrapes. Paired samples were collected from 103 patients diagnosed with stage I to IV endometrial cancer. Urine and self-samples were collected at home. All samples were tested for nine DNA methylation markers using quantitative methylation-specific PCR. Methylation levels measured in endometrial cancer patients were compared to unpaired samples of 317 healthy controls. Diagnostic performances were evaluated by univariable and multivariable logistic regression analysis, followed by leave-one-out cross-validation. Each methylation marker showed significantly higher methylation levels in all sample types of endometrial cancer patients compared to healthy controls (P <.01). Optimal three-marker combinations demonstrated excellent diagnostic performances with area under the receiver operating curve values of 0.95 (95% CI: 0.92-0.98), 0.94 (0.90-0.97) and 0.97 (0.96-0.99), for endometrial cancer detection in urine, self-samples and scrapes, respectively. Sensitivities ranged from 89% to 93% at specificities of 90% to 92%. Virtually equal performances were obtained after cross-validation and excellent diagnostic performances were maintained for stage I endometrial cancer detection. Our study shows the value of methylation analysis in patient-friendly sample types for endometrial cancer detection of all stages. This approach has great potential to screen patient populations at risk for endometrial cancer.
AB - Endometrial cancer incidence is rising and current diagnostics often require invasive biopsy procedures. DNA methylation marker analysis of minimally- and non-invasive sample types could provide an easy-to-apply and patient-friendly alternative to determine cancer risk. Here, we compared the performance of DNA methylation markers to detect endometrial cancer in urine, cervicovaginal self-samples and clinician-taken cervical scrapes. Paired samples were collected from 103 patients diagnosed with stage I to IV endometrial cancer. Urine and self-samples were collected at home. All samples were tested for nine DNA methylation markers using quantitative methylation-specific PCR. Methylation levels measured in endometrial cancer patients were compared to unpaired samples of 317 healthy controls. Diagnostic performances were evaluated by univariable and multivariable logistic regression analysis, followed by leave-one-out cross-validation. Each methylation marker showed significantly higher methylation levels in all sample types of endometrial cancer patients compared to healthy controls (P <.01). Optimal three-marker combinations demonstrated excellent diagnostic performances with area under the receiver operating curve values of 0.95 (95% CI: 0.92-0.98), 0.94 (0.90-0.97) and 0.97 (0.96-0.99), for endometrial cancer detection in urine, self-samples and scrapes, respectively. Sensitivities ranged from 89% to 93% at specificities of 90% to 92%. Virtually equal performances were obtained after cross-validation and excellent diagnostic performances were maintained for stage I endometrial cancer detection. Our study shows the value of methylation analysis in patient-friendly sample types for endometrial cancer detection of all stages. This approach has great potential to screen patient populations at risk for endometrial cancer.
KW - DNA methylation
KW - cervical scrape
KW - endometrial cancer
KW - urine
KW - vaginal sample
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85150881504&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/36912267
UR - http://www.scopus.com/inward/record.url?scp=85150881504&partnerID=8YFLogxK
U2 - 10.1002/ijc.34504
DO - 10.1002/ijc.34504
M3 - Article
C2 - 36912267
SN - 0020-7136
VL - 153
SP - 341
EP - 351
JO - International journal of cancer
JF - International journal of cancer
IS - 2
ER -