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Multilayered Epigenetic Analysis Identifies a Molecular Portrait for Psychological Resilience in Patients With Breast Cancer

Richter, Corinna LU ; Dethlefsen, Olga ; Axelsson, Ulrika LU orcid ; Lundberg, Kristina LU ; Rydén, Lisa LU orcid ; Johnsson, Per LU ; Ringdahl, Ulrika LU ; Hallberg, Ingalill Rahm LU and Borrebaeck, Carl A.K. LU (2025) In Biological Psychiatry Global Open Science 5(5).
Abstract

Background: Psychological resilience refers to a person's positive adaptation when faced with adversities, such as a breast cancer (BC) diagnosis. Highly resilient patients are more likely to regain stability and be protected from health conditions such as depression, anxiety, and posttraumatic stress disorder. We aimed to identify epigenetic markers that distinguish high- and low-resilient patients in a BC cohort at time of diagnosis. Methods: Genome-wide DNA methylation was determined in participants selected from a prospectively collected cohort of 1040 newly diagnosed BC patients with known resilience status. DNA methylation of those displaying the highest and lowest scores (n = 425), as measured by the Connor-Davidson Resilience... (More)

Background: Psychological resilience refers to a person's positive adaptation when faced with adversities, such as a breast cancer (BC) diagnosis. Highly resilient patients are more likely to regain stability and be protected from health conditions such as depression, anxiety, and posttraumatic stress disorder. We aimed to identify epigenetic markers that distinguish high- and low-resilient patients in a BC cohort at time of diagnosis. Methods: Genome-wide DNA methylation was determined in participants selected from a prospectively collected cohort of 1040 newly diagnosed BC patients with known resilience status. DNA methylation of those displaying the highest and lowest scores (n = 425), as measured by the Connor-Davidson Resilience Scale, was analyzed in whole blood, using a multilayered bioinformatic approach. Sample subsets were created to identify differentially methylated probes (DMPs) and differentially methylated regions (DMRs), and fold change and area size were used to estimate the strength of methylation differences. The key regions associated with psychological resilience allowed us to build a classifier, using a random forest model, which was validated using an independent cohort (n = 80). Results: DMPs and DMRs that consistently distinguished samples derived from high- and low-resilient patients were identified, and methylation differences followed a dose-response pattern related to resilience levels. DMRs included LY6G5C, ZFP57, CDH9, ZNF727, and C8orf31, where LY6G5C was found to be the most consistent DMR. Psychological resilience status could be predicted in the independent cohort with an area under the curve of 0.74 and a sensitivity and specificity of 0.67 and 0.72, respectively. Conclusions: LY6G5C was identified as a novel marker for psychological resilience, paving the way for a more conceptual and comprehensive molecular understanding.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bioinformatics, Biomarker, Breast cancer, DNA methylation, Epigenetics, Psychological resilience
in
Biological Psychiatry Global Open Science
volume
5
issue
5
article number
100545
publisher
Elsevier
external identifiers
  • pmid:40697488
  • scopus:105010336607
ISSN
2667-1743
DOI
10.1016/j.bpsgos.2025.100545
language
English
LU publication?
yes
id
3a819f69-09d3-45d4-bd47-0b533e00ee90
date added to LUP
2025-11-04 12:46:20
date last changed
2025-11-05 03:05:46
@article{3a819f69-09d3-45d4-bd47-0b533e00ee90,
  abstract     = {{<p>Background: Psychological resilience refers to a person's positive adaptation when faced with adversities, such as a breast cancer (BC) diagnosis. Highly resilient patients are more likely to regain stability and be protected from health conditions such as depression, anxiety, and posttraumatic stress disorder. We aimed to identify epigenetic markers that distinguish high- and low-resilient patients in a BC cohort at time of diagnosis. Methods: Genome-wide DNA methylation was determined in participants selected from a prospectively collected cohort of 1040 newly diagnosed BC patients with known resilience status. DNA methylation of those displaying the highest and lowest scores (n = 425), as measured by the Connor-Davidson Resilience Scale, was analyzed in whole blood, using a multilayered bioinformatic approach. Sample subsets were created to identify differentially methylated probes (DMPs) and differentially methylated regions (DMRs), and fold change and area size were used to estimate the strength of methylation differences. The key regions associated with psychological resilience allowed us to build a classifier, using a random forest model, which was validated using an independent cohort (n = 80). Results: DMPs and DMRs that consistently distinguished samples derived from high- and low-resilient patients were identified, and methylation differences followed a dose-response pattern related to resilience levels. DMRs included LY6G5C, ZFP57, CDH9, ZNF727, and C8orf31, where LY6G5C was found to be the most consistent DMR. Psychological resilience status could be predicted in the independent cohort with an area under the curve of 0.74 and a sensitivity and specificity of 0.67 and 0.72, respectively. Conclusions: LY6G5C was identified as a novel marker for psychological resilience, paving the way for a more conceptual and comprehensive molecular understanding.</p>}},
  author       = {{Richter, Corinna and Dethlefsen, Olga and Axelsson, Ulrika and Lundberg, Kristina and Rydén, Lisa and Johnsson, Per and Ringdahl, Ulrika and Hallberg, Ingalill Rahm and Borrebaeck, Carl A.K.}},
  issn         = {{2667-1743}},
  keywords     = {{Bioinformatics; Biomarker; Breast cancer; DNA methylation; Epigenetics; Psychological resilience}},
  language     = {{eng}},
  number       = {{5}},
  publisher    = {{Elsevier}},
  series       = {{Biological Psychiatry Global Open Science}},
  title        = {{Multilayered Epigenetic Analysis Identifies a Molecular Portrait for Psychological Resilience in Patients With Breast Cancer}},
  url          = {{http://dx.doi.org/10.1016/j.bpsgos.2025.100545}},
  doi          = {{10.1016/j.bpsgos.2025.100545}},
  volume       = {{5}},
  year         = {{2025}},
}