A Multi-Omics Study of the Effect and Mechanisms of Acupuncture on Psychoneurological Symptoms Among Breast Cancer Survivors

针灸对乳腺癌幸存者心理神经症状的影响和机制的多组学研究

• 批准号: 10649197
• 负责人: Hongjin Li
• 金额: $ 18.69万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-11 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10649197
• 关键词: Acupuncture Therapy; Affect; Arthralgia; Biological Markers; Breast Cancer survivor; Cancer Survivor; Caring; Disease; Distress; Enrollment; Fatigue; Future; Glutamate Metabolism Pathway; Goals; Health; High Pressure Liquid Chromatography; Homeostasis; Hot flushes; Hypertension; Individual; Inflammation; Integrative Therapy; Intervention; Knowledge; Kynurenic Acid; Kynurenine; Malignant Neoplasms; Mental Depression; Metabolic; Metabolic Pathway; Metabolic dysfunction; Metabolism; National Cancer Institute; Outcome; Pain; Pathway interactions; Personal Satisfaction; Phenotype; Play; Polypharmacy; Population; Protocols documentation; Quality of life; Quinolinic Acid; Randomized, Controlled Trials; Regulation; Reporting; Ribosomal RNA; Risk; Role; Science; Serotonin; Serum; Severities; Sleep disturbances; Symptoms; Time; Tryptophan; Tryptophan Metabolism Pathway; Validation; acceptability and feasibility; associated symptom; biomarker signature; cancer therapy; clinical application; clinical practice; cost; effective intervention; fatty acid biosynthesis; fecal metabolome; fecal microbiome; functional status; gut microbiome; gut microbiota; immune function; improved; innovation; liquid chromatography mass spectrometry; metabolome; metabolomics; microbiome; microbiome research; microbiota; multiple omics; novel; novel marker; pain score; personalized intervention; phase II trial; primary outcome; reduce symptoms; response; secondary outcome; symptom cluster; symptom management; systematic review

ABSTRACT A large proportion of breast cancer survivors—24% to 68% of them—report co-occurring psychoneurological (PN) symptoms or the PN symptom cluster (defined as a cluster of pain, fatigue, and sleep disturbance) during and after cancer treatment. Acupuncture is a safe and holistic treatment known to relieve cancer-related symptoms, including PN symptoms. However, its role and mechanism in treating multiple PN symptoms simultaneously remains unclear. Metabolomics can reveal systematic metabolic changes and time-effect relationships between an intervention and the targeted disease. Metabolomic studies suggest that the tryptophan (Trp)–kynurenine (Kyn) metabolic pathway plays a critical role in PN symptoms among cancer survivors. It remains unknown whether the effect of acupuncture on PN symptoms is associated with regulation of the inflammation-induced activation of the Trp-Kyn pathway or is associated with other novel pathways. This R21’s innovative approach to these outstanding questions involves performing an integrated analysis of breast cancer survivors’ serum and fecal metabolome and microbiome before and after an acupuncture intervention. The goal is to understand the effect and mechanism of acupuncture in treating the PN symptom cluster among breast cancer survivors. The specific aims are: (1) to evaluate whether a 5-week acupuncture intervention decreases the severity of the PN symptom cluster (a composite score of pain, fatigue, and sleep disturbance), as well as each of the 3 individual PN symptoms, among breast cancer survivors; (2) to determine whether the hypothesized decrease in the severity of the PN symptom cluster and each PN symptom following acupuncture is associated with changes in targeted Trp-Kyn pathway metabolites; and (3) to explore associations between changes in untargeted biomarkers in the serum and fecal metabolome and gut microbiome and the changes in the PN symptom cluster and each PN symptom. We hypothesize that acupuncture will reduce the PN symptom cluster through the Trp-Kyn metabolomic pathway and will also influence and produce other beneficial changes in the metabolome and microbiome. This integration of large-scale metabolomics and microbiome markers with PN symptom phenotypes will advance a mechanistic understanding of acupuncture and identify novel biomarkers that could be used in future studies of personalized acupuncture approaches to symptom management and relief among breast cancer survivors.

抽象的 大部分乳腺癌的存活率（其中24％至68％ （PN）症状或PN症状簇（定义为疼痛，疲劳和睡眠障碍） 并在癌症治疗后。针灸是一种安全，整体的治疗方法，已知可以挽救与癌症有关的 症状，包括PN症状。但是，它在治疗多种PN症状方面的作用和机制 同样，尚不清楚。代谢组学可以揭示系统的代谢变化和时间效应 干预与目标疾病之间的关系。代谢组学研究表明 色氨酸（TRP）–Kynurenine（Kyn）代谢途径在癌症的PN症状中起关键作用 幸存者。针灸对PN症状的影响是否与调节有关，尚不清楚 炎症引起的TRP-KYN途径的激活或与其他新型途径相关的。这 R21针对这些杰出问题的创新方法涉及对乳房进行综合分析 针灸干预前后，癌症幸存者的血清和粪便代谢组和微生物组。 目的是了解针灸治疗PN症状簇的效果和机制 乳腺癌存活。具体目的是：（1）评估是否进行5周的针灸干预 减少PN症状簇的严重程度（疼痛，疲劳和睡眠障碍的综合评分）， 以及三种单个PN症状中的每一个，在乳腺癌的存活中； （2）确定是否 假设降低PN症状簇的严重程度和针灸后的每种PN症状 与靶向TRP-KYN途径代谢产物的变化有关； （3）探索之间的关联 血清和粪便代谢组和肠道微生物组中未靶向的生物标志物的变化以及变化 PN症状簇和每个PN症状。我们假设针灸会减轻PN症状 通过TRP-KYN代谢组途径聚集，还将影响和产生其他有益的变化 在代谢组和微生物组中。大规模代谢组学和微生物组标记的这种整合与 PN症状表型将提高对针灸的机械理解并识别新颖 可以在未来的个性化针灸方法研究中使用的生物标志物 乳腺癌存活中的管理和缓解。