Investigating Molecular-Genetic Correlates of Fatigue

虽然疲劳的潜在机制已经在几种疾病情况下进行了研究，但其病因、机制和危险因素仍然不清楚，目前这种症状仍然处理不善。已经进行了与癌症患者治疗相关的疲劳的纵向研究，但显示癌症治疗前后分子机制变化的数据有限，这些数据可以识别在治疗过程中和治疗后有可能经历疲劳的个体。疲劳是一种多维症状，包括时间、感觉、认知/心理、情感/情绪、行为和生理等多个维度。这项前瞻性的观察性研究将探索接受各种治疗(如免疫治疗、激素治疗和化疗)的癌症患者疲劳的分子遗传学机制。 这项研究的主要目的是描述癌症患者在癌症治疗前、治疗中和治疗后所经历的自我报告的疲劳、抑郁和健康相关生活质量(HRQOL)的变化。这项研究的次要目标是调查促炎细胞因子(肿瘤坏死因子、胰岛素样生长因子-I、白介素6、白介素8、转化生长因子和转化生长因子)的变化，确定癌症治疗前、中、后外周血和组织样本中基因表达的变化，以及这些生物标记物水平的变化与自我报告的疲劳、抑郁和HRQOL评分的关系。这项研究还旨在测量患者在癌症治疗之前、期间和完成治疗时的骨骼肌力、认知功能、活动水平和能量消耗，并将这些发现与自我报告的疲劳、抑郁和HRQOL评分相关联。

Although the underlying mechanisms of fatigue have been studied in several disease conditions, the etiology, mechanisms, and risk factors remain elusive, and this symptom remains poorly managed at present. Longitudinal studies related to treatment-related fatigue in cancer patients have been conducted, but there are limited data showing changes in molecular mechanisms before and after cancer therapy which can identify individuals who are at risk to experience fatigue during and after therapy. Fatigue is conceptualized as a multidimensional symptom which incorporates temporal, sensory, cognitive/mental, affective/emotional, behavioral, and physiological dimensions. This prospective, observational study will explore the molecular-genetic mechanisms underlying fatigue experienced by cancer patients receiving various therapies (e.g. immune therapy, hormone therapy, and chemotherapy). The primary objective of the study is to describe the changes in the self-reported fatigue, depression, and health-related quality of life (HRQOL) experienced by cancer patients before, during, and after cancer therapy. The secondary objectives of this study are to investigate the pro-inflammatory cytokine profile (TNF, IGF-I, IL-6, IL-8, TGF and ), determine changes in gene expression from peripheral blood and tissue samples before, during, and after cancer treatment and to relate changes in the levels of these biological markers to self-reported fatigue, depression, and HRQOL scores. This study also aims to measure the skeletal muscle strength, cognitive function, activity levels and energy expenditure of patients before, during, and at completion of cancer treatment and relate these findings with self-reported fatigue, depression, and HRQOL scores.