DNA methylation in normal-appearing tissue associated with prostate cancer recurrence and metastasis

Abstract There is a need for more precise biomarkers and understanding on the development of aggressive prostate cancer. In this study, we analyzed DNA methylation in 64 prostate cancer tissue samples, using tissue from radical prostatectomy patients (n = 16) with up to 16 years of clinical follow-u...

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Main Authors: Christine Aaserød Pedersen, Thomas Fleischer, Maximilian Wess, Elise Midtbust, Maria K. Andersen, Trond Viset, Øystein Størkersen, Morten B. Rye, May-Britt Tessem
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Clinical Epigenetics
Online Access:https://doi.org/10.1186/s13148-025-01932-x
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author Christine Aaserød Pedersen
Thomas Fleischer
Maximilian Wess
Elise Midtbust
Maria K. Andersen
Trond Viset
Øystein Størkersen
Morten B. Rye
May-Britt Tessem
author_facet Christine Aaserød Pedersen
Thomas Fleischer
Maximilian Wess
Elise Midtbust
Maria K. Andersen
Trond Viset
Øystein Størkersen
Morten B. Rye
May-Britt Tessem
author_sort Christine Aaserød Pedersen
collection DOAJ
description Abstract There is a need for more precise biomarkers and understanding on the development of aggressive prostate cancer. In this study, we analyzed DNA methylation in 64 prostate cancer tissue samples, using tissue from radical prostatectomy patients (n = 16) with up to 16 years of clinical follow-up. We used several samples from each patient including both normal and cancer tissue to study DNA methylation patterns in relation to aggressiveness measured by follow-up data of biochemical recurrence and metastasis status as clinical endpoints. We identified differentially methylated CpGs associated with recurrence and metastasis, regardless of whether the tissue was normal, cancer-adjacent normal, or cancer. The identified CpG sites were over-represented in promoter regions and transcription factor binding regions, suggesting their influence on gene expression regulation. They further exhibited low intrapatient heterogeneity both between normal, normal adjacent, and cancer tissue, making them favorable as potential biomarkers for aggressive prostate cancer. However, validation of a subset of these CpGs in an external dataset was unsuccessful.
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spelling doaj-art-ab0f17274ead492eb157771d8b96cfb32025-08-20T04:02:54ZengBMCClinical Epigenetics1868-70832025-07-0117111210.1186/s13148-025-01932-xDNA methylation in normal-appearing tissue associated with prostate cancer recurrence and metastasisChristine Aaserød Pedersen0Thomas Fleischer1Maximilian Wess2Elise Midtbust3Maria K. Andersen4Trond Viset5Øystein Størkersen6Morten B. Rye7May-Britt Tessem8Department of Circulation and Medical Imaging, NTNUDepartment of Cancer Genetics, Institute for Cancer Research, Oslo University HospitalDepartment of Circulation and Medical Imaging, NTNUDepartment of Circulation and Medical Imaging, NTNUDepartment of Circulation and Medical Imaging, NTNUDepartment of Pathology, St. Olav Hospital, Trondheim University HospitalDepartment of Pathology, St. Olav Hospital, Trondheim University HospitalDepartment of Clinical and Molecular Medicine, NTNUDepartment of Circulation and Medical Imaging, NTNUAbstract There is a need for more precise biomarkers and understanding on the development of aggressive prostate cancer. In this study, we analyzed DNA methylation in 64 prostate cancer tissue samples, using tissue from radical prostatectomy patients (n = 16) with up to 16 years of clinical follow-up. We used several samples from each patient including both normal and cancer tissue to study DNA methylation patterns in relation to aggressiveness measured by follow-up data of biochemical recurrence and metastasis status as clinical endpoints. We identified differentially methylated CpGs associated with recurrence and metastasis, regardless of whether the tissue was normal, cancer-adjacent normal, or cancer. The identified CpG sites were over-represented in promoter regions and transcription factor binding regions, suggesting their influence on gene expression regulation. They further exhibited low intrapatient heterogeneity both between normal, normal adjacent, and cancer tissue, making them favorable as potential biomarkers for aggressive prostate cancer. However, validation of a subset of these CpGs in an external dataset was unsuccessful.https://doi.org/10.1186/s13148-025-01932-x
spellingShingle Christine Aaserød Pedersen
Thomas Fleischer
Maximilian Wess
Elise Midtbust
Maria K. Andersen
Trond Viset
Øystein Størkersen
Morten B. Rye
May-Britt Tessem
DNA methylation in normal-appearing tissue associated with prostate cancer recurrence and metastasis
Clinical Epigenetics
title DNA methylation in normal-appearing tissue associated with prostate cancer recurrence and metastasis
title_full DNA methylation in normal-appearing tissue associated with prostate cancer recurrence and metastasis
title_fullStr DNA methylation in normal-appearing tissue associated with prostate cancer recurrence and metastasis
title_full_unstemmed DNA methylation in normal-appearing tissue associated with prostate cancer recurrence and metastasis
title_short DNA methylation in normal-appearing tissue associated with prostate cancer recurrence and metastasis
title_sort dna methylation in normal appearing tissue associated with prostate cancer recurrence and metastasis
url https://doi.org/10.1186/s13148-025-01932-x
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