title: Upregulation of α-synuclein during localized radiation therapy signals the association of cancer-related fatigue with the activation of inflammatory and neuroprotective pathways.
abstract: OBJECTIVE
  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).
  
  
  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 peripheral 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Institute of Nursing Research, National Institutes of Health, Bethesda, MD 20892, USA. saliganl@mail.nih.gov
authors.forename: L N
authors.initials: LN
authors.lastname: Saligan
authors.forename: C P
authors.initials: CP
authors.lastname: Hsiao
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: X M
authors.initials: XM
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: St John
authors.forename: A
authors.initials: A
authors.lastname: Kaushal
authors.forename: D
authors.initials: D
authors.lastname: Citrin
authors.forename: J J
authors.initials: JJ
authors.lastname: Barb
authors.forename: P J
authors.initials: PJ
authors.lastname: Munson
authors.forename: R A
authors.initials: RA
authors.lastname: Dionne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005221:Fatigue / Q000209:etiology / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000150:complications / Q000532:radiotherapy*; D012333:RNA, Messenger / Q000032:analysis*; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C497604:SNCA protein, human; D051844:alpha-Synuclein