Richter Corinna, Dethlefsen Olga, Axelsson Ulrika, Lundberg Kristina, Rydén Lisa, Johnsson Per, Ringdahl Ulrika, Hallberg Ingalill Rahm, Borrebaeck Carl A K
CREATE Health Translational Cancer Center, Department of Immunotechnology, Lund University, Lund, Sweden.
National Bioinformatics Infrastructure, Science for Life Laboratory, Stockholm University, Stockholm, Sweden.
Biol Psychiatry Glob Open Sci. 2025 Jun 3;5(5):100545. doi: 10.1016/j.bpsgos.2025.100545. eCollection 2025 Sep.
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.
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 ( = 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 ( = 80).
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 , and , where 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.
was identified as a novel marker for psychological resilience, paving the way for a more conceptual and comprehensive molecular understanding.
心理韧性是指一个人在面对逆境（如乳腺癌诊断）时的积极适应能力。高心理韧性的患者更有可能恢复稳定，并免受抑郁症、焦虑症和创伤后应激障碍等健康问题的影响。我们旨在识别在乳腺癌队列诊断时区分高心理韧性和低心理韧性患者的表观遗传标记。
对从1040名新诊断的已知心理韧性状态的乳腺癌患者前瞻性收集的队列中选取的参与者进行全基因组DNA甲基化测定。使用多层生物信息学方法，在全血中分析通过康纳 - 戴维森韧性量表测量显示最高和最低分数（= 425）的患者的DNA甲基化情况。创建样本子集以识别差异甲基化探针（DMP）和差异甲基化区域（DMR），并使用倍数变化和区域大小来估计甲基化差异的强度。与心理韧性相关的关键区域使我们能够使用随机森林模型构建一个分类器，并使用独立队列（= 80）进行验证。
识别出了始终能区分高心理韧性和低心理韧性患者样本的DMP和DMR，甲基化差异遵循与韧性水平相关的剂量反应模式。DMR包括 ， ，其中 被发现是最一致的DMR。在独立队列中可以预测心理韧性状态，曲线下面积为0.74，敏感性和特异性分别为0.67和0.72。
被确定为心理韧性的一种新标记，为更具概念性和综合性的分子理解铺平了道路。
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