Purpose Neuroinflammatory mechanisms are associated with fatigue in neurodegenerative conditions such as Parkinson’s. The symptoms in Parkinson’s including fatigue are thought to be related to α-synuclein overexpression. This study investigated genomic correlates of fatigue experienced by men with prostate cancer receiving external beam radiation therapy (EBRT). Patients and Methods Sixteen men with non-metastatic prostate cancer who were scheduled to receive EBRT were enrolled. Fatigue scores and blood were obtained at baseline (prior to EBRT, D0); one hour following initiation of EBRT (D1), day 7 (D7), day 14 (D14), midpoint (days 19–21, D21), completion (days 38–42, D42), and four weeks post EBRT (days 68–72, D72). Gene expression profiling using microarray analysis was performed from whole blood and confirmatory qPCR and protein (ELISA) analyses verified the microarray results. Correlations between fatigue and gene/protein expressions were determined using a mixed model approach. Results Microarray data showed significant, differential expression of 463 probesets following EBRT. SNCA had a 2.95 fold change at D21 from baseline. SNCA expression was confirmed by qPCR (p < 0.001) and ELISA (p < 0.001) over time during EBRT. Fatigue scores were significantly correlated with SNCA gene expression on D14 (r = 0.55, p < 0.05) and plasma α-synuclein concentrations on D42 of EBRT (r = 0.54, p = 0.04). Conclusion Fatigue experienced during EBRT may be mediated by α-synuclein overexpression. Alpha-synuclein may serve as a useful biomarker to understand the mechanisms and pathways related to the development of fatigue in this population.

Results provide information on effective strategies that patients with prostate cancer found to reduce their symptoms. The strategies used provide a foundation for developing and testing interventions for personalised symptom management.

Fatigue is a prevalent symptom associated with decreased quality of life and increased mortality in individuals with end stage renal disease (ESRD), yet causes of fatigue in individuals with ESRD remain poorly understood. We examined gene expression of Neuronal PAS Domain Protein 2 (NPAS2) in relation to patient-reported fatigue in 122 individuals with ESRD. Independent samples t-tests were used to examine NPAS2 gene expression profiles of: non-fatigue versus fatigue. Multivariable regression analyses were used to examine the relationship between fatigue and numerous variables including depression. Participants were approximately 58 years old (+/- 13.2 years), 78% African American ( n = 95), and 72% male ( n = 88). The phenotype of fatigue was not significantly associated with gene expression of NPAS2 but was significantly associated with depression ( p< .001). This study suggests that further research should examine the causal mechanism between depression and fatigue in order to identify genetic factors that could explain the high comorbidity of depression and fatigue.

Fatigue is one of the most common side-effects accompanying radiotherapy, but arguably the least understood. Radiotherapy-induced fatigue (RIF) is a clinical subtype of cancer treatment-related fatigue. It is described as a pervasive, subjective sense of tiredness persisting over time, interferes with activities of daily living, and is not relieved by adequate rest or sleep. RIF is one of the early side-effects and long-lasting for cancer patients treated with localized radiation. Although the underlying mechanisms of fatigue have been studied in several disease conditions, the etiology, mechanisms, and risk factors of RIF remain elusive, and this symptom remains poorly managed. The purpose of this paper is to review and discuss recent articles that defined, proposed biologic underpinnings and mechanisms to explain the pathobiology of RIF, as well as articles that proposed interventions to manage RIF. Understanding the mechanisms of RIF can describe promising pathways to identify at-risk individuals and identify potential therapeutic targets to alleviate and prevent RIF using a multimodal, multidisciplinary approach.