A Data-Driven Epigenetic Characterization of Morning Fatigue Severity in Oncology Patients Receiving Chemotherapy: Associations With Epigenetic Age Acceleration, Blood Cell Types, and Expression-Associated Methylation

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-07-25 DOI:10.1002/cam4.71067

Caroline Le, Maureen Lewis, Carolyn S. Harris, Liam Berger, Esther Chavez-Iglesias, Lisa Morse, Anatol Sucher, Ritu Roy, Adam Olshen, Marilyn J. Hammer, Steve Paul, Margaret Wallhagen, Raymond Chan, Michael Sayer, Sue Yom, Nam-Woo Cho, Alexandre Chan, Jon Levine, Anand Dhruva, Christine Miaskowski, Yvette P. Conley, Kord M. Kober

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引用次数: 0

Abstract

Background

Moderate-to-severe fatigue commonly occurs in patients with cancer. Given the numerous roles that epigenetic processes may play in the development and severity of fatigue, the purposes of this study were to (1) use a data-driven discovery approach to evaluate for mechanisms underlying morning fatigue in a group of oncology patients receiving chemotherapy and (2) identify common biological mechanisms associated with morning fatigue severity across these independent epigenetic evaluations.

Methods

Patients completed questionnaires during the week prior to their chemotherapy treatment. Severity of morning fatigue was evaluated using the Lee Fatigue Scale. Associations between morning fatigue severity and epigenetic aging acceleration (EAA), immune cell type compositions, and differential methylation of expression-associated loci (eCpGs) in distal regions (i.e., upstream of a gene on the same chromosome) were evaluated. These results were then evaluated for common biological mechanisms.

Results

High morning fatigue was associated with older epigenetic age, positive EAA, and higher levels of EAA. Patients of the “Fast ager” type were more likely to have high morning fatigue. Higher morning fatigue was associated with lower (CD4 memory, CD8 memory, and NK) and higher (neutrophil and T regulatory) estimated proportions of cell types. Morning fatigue severity was associated with one differentially methylated distal region containing five eCpGs mapping to three genes (i.e., CILP, ONECUT1, SLCO3A1). Preliminary support was found for the role of Inflammaging as a common biological mechanism for morning fatigue.

Conclusions

This study provides an epigenetic characterization of morning fatigue in patients receiving chemotherapy. The findings suggest that biological aging, gene regulatory, and inflammatory processes may contribute to morning fatigue and provide future targets for therapeutic interventions.

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接受化疗的肿瘤患者早晨疲劳严重程度的数据驱动的表观遗传学特征：与表观遗传年龄加速、血细胞类型和表达相关的甲基化相关

背景：中度至重度疲劳常见于癌症患者。鉴于表观遗传过程在疲劳的发展和严重程度中可能发挥的众多作用，本研究的目的是：(1)使用数据驱动的发现方法来评估一组接受化疗的肿瘤患者早晨疲劳的机制；(2)通过这些独立的表观遗传评估确定与早晨疲劳严重程度相关的共同生物学机制。方法患者于化疗前一周完成问卷调查。采用李氏疲劳量表评估晨疲劳的严重程度。研究人员评估了早晨疲劳严重程度与表观遗传衰老加速（EAA）、免疫细胞类型组成和远端区域（即同一染色体上的基因上游）表达相关位点（ecpg）差异甲基化之间的关系。然后对这些结果进行了常见生物学机制的评估。结果晨疲劳与表观遗传年龄较大、EAA阳性、EAA水平较高有关。“快老”型患者更容易出现晨间疲劳。较高的早晨疲劳与较低的（CD4记忆、CD8记忆和NK）和较高的（中性粒细胞和T调节）细胞类型的估计比例相关。早晨疲劳的严重程度与一个差异甲基化的远端区域有关，该区域包含五个与三个基因（即CILP， ONECUT1, SLCO3A1）相关的ecpg。初步支持炎症作为早晨疲劳的常见生物机制的作用。结论本研究提供了化疗患者早晨疲劳的表观遗传学特征。研究结果表明，生物衰老、基因调控和炎症过程可能导致早晨疲劳，并为治疗干预提供了未来的目标。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.