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

Area of Science:

• Epigenetics
• Genomics
• Cancer Research

Background:

• Psychological resilience aids adaptation to adversities like breast cancer (BC) diagnosis.
• High resilience protects against depression, anxiety, and PTSD in BC patients.
• Identifying epigenetic markers can differentiate resilience levels in BC survivors.

Purpose of the Study:

• To identify epigenetic markers distinguishing high and low psychological resilience in BC patients.
• To explore the role of DNA methylation in BC patient resilience.
• To develop a predictive model for resilience status.

Main Methods:

• Genome-wide DNA methylation analysis in whole blood of BC patients.
• Selection of patients with highest and lowest resilience scores (n=425) based on Connor-Davidson Resilience Scale.
• Bioinformatic analysis to identify differentially methylated probes (DMPs) and regions (DMRs), including a random forest classifier validated in an independent cohort (n=80).

Main Results:

• Identified DMPs and DMRs consistently differentiating high and low resilience.
• Observed a dose-response pattern in methylation differences related to resilience.
• LY6G5C emerged as the most consistent DMR, with a predictive classifier achieving an AUC of 0.74 in an independent cohort.

Conclusions:

• LY6G5C is a novel epigenetic marker for psychological resilience.
• This finding contributes to a molecular understanding of resilience in the context of breast cancer.
• Epigenetic profiling may offer insights into patient adaptation and well-being.