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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的很大一部分乳腺癌幸存者（其中 24% 至 68%）报告同时存在心理神经问题 (PN) 症状或 PN 症状群（定义为一系列疼痛、疲劳和睡眠障碍）癌症治疗后，针灸是一种安全且全面的治疗方法，可以缓解癌症相关症状。然而，其在治疗多种 PN 症状中的作用和机制。同时代谢组学能否揭示系统代谢变化和时间效应仍不清楚。干预措施与目标疾病之间的关系。色氨酸 (Trp)-犬尿氨酸 (Kyn) 代谢途径在癌症 PN 症状中发挥关键作用目前尚不清楚针灸对 PN 症状的影响是否与调节有关。炎症诱导的 Trp-Kyn 通路激活或与其他新通路相关。 R21 针对这些突出问题的创新方法包括对乳房进行综合分析癌症幸存者针灸干预前后的血清和粪便代谢组和微生物组。目的是了解针灸治疗 PN 症状群的效果和机制。乳腺癌幸存者的具体目的是：（1）评估是否需要进行5周的针灸干预。降低 PN 症状群的严重程度（疼痛、疲劳和睡眠障碍的综合评分），以及乳腺癌幸存者中的 3 种 PN 症状中的每一种，以确定是否针刺后 PN 症状群和每个 PN 症状的严重程度减轻与目标 Trp-Kyn 通路代谢物的变化相关；(3) 探索之间的关联；血清和粪便代谢组和肠道微生物组中非靶向生物标志物的变化以及 PN 症状群和每个 PN 症状我们相信针灸会减轻 PN 症状。通过 Trp-Kyn 代谢途径聚集，还将影响和产生其他有益的变化大规模代谢组学和微生物组标记的整合。 PN 症状表型将促进对针灸机制的理解并识别新的治疗方法可用于未来针对症状的个性化针灸方法研究的生物标志物乳腺癌幸存者的管理和缓解。