title: Mitochondria-related gene expression changes are associated with fatigue in patients with nonmetastatic prostate cancer receiving external beam radiation therapy.
abstract: BACKGROUND
  Cancer-related fatigue (CRF) is associated with negative health outcomes and decreased health-related quality of life; however, few longitudinal studies have investigated molecular-genetic mechanisms of CRF.
  
  
  OBJECTIVE
  The objective of this study was to describe relationships between mitochondria-related gene expression changes and self-reported fatigue in prostate cancer patients receiving external beam radiation therapy (EBRT).
  
  
  METHODS
  A prospective, exploratory, and repeated-measures design was used. Self-report questionnaires and peripheral whole-blood samples were collected from 15 patients at 7 time points. Baseline data were compared against 15 healthy controls. The Human Mitochondria RT Profiler PCR Array was used to identify differential regulation of genes involved in mitochondrial biogenesis and function.
  
  
  RESULTS
  Compared with baseline, there were significant increases in fatigue scores (P = .02-.04) and changes in mitochondria-related gene expression (P = .001-.05) over time. Mean fatigue scores were 1.66 (SD, 1.66) at baseline, 3.06 (SD, 1.95) at EBRT midpoint, 2.98 (SD, 2.20) at EBRT completion, and 2.64 (SD, 2.56) at 30 days after EBRT. Over time, 11 genes related to mitochondrial function and structure were differentially expressed. Of these 11 genes, 3 (BCL2L1, FIS1, SLC25A37) were more than 2.5 fold up-regulated, and 8 (AIFM2, BCL2, IMMP2L, MIPEP, MSTO1, NEFL, SLC25A23, SLC25A4) were greater than 2-fold down-regulated. Furthermore, 8 genes (AIFM2, BCL2, FIS1, IMMP2L, MSTO1, SLC25A23, SLC25A37, SLC25A4) were significantly associated with the changes in fatigue scores.
  
  
  CONCLUSIONS
  This study provides preliminary evidence that 8 mitochondrial function genes were significantly associated with fatigue in prostate cancer patients during EBRT.
  
  
  CONCLUSIONS
  These findings identify possible pathways and early biomarkers for targeting novel interventions for CRF.
authors.affiliation: National Institute of Nursing Research, National Institutes of Health, Bethesda, Maryland 20892, USA. hsiaoc@mail.nih.gov
authors.forename: Chao-Pin
authors.initials: CP
authors.lastname: Hsiao
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Aradhana
authors.initials: A
authors.lastname: Kaushal
authors.forename: Leorey
authors.initials: L
authors.lastname: Saligan
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000378:metabolism; D017920:Antiporters / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001918:Brachytherapy / Q000451:nursing*; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D015536:Down-Regulation; D010450:Endopeptidases / Q000378:metabolism; D005221:Fatigue / Q000175:diagnosis / Q000209:etiology / Q000451:nursing*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000451:nursing* / Q000532:radiotherapy; D057566:Self Report; D011795:Surveys and Questionnaires; D015854:Up-Regulation; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C462504:ferroptosis suppressor protein 1, human; C086357:ATP-Mg-Pi carrier proteins, mitochondria; D033741:Adenine Nucleotide Translocator 1; D017920:Antiporters; D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; D027682:Cation Transport Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C476525:FIS1 protein, human; C519909:MSTO1 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D016900:Neurofilament Proteins; C580832:SLC25A4 protein, human; C561492:Slc25a37 protein, human; D051020:bcl-X Protein; C044882:neurofilament protein L; D010450:Endopeptidases; C425070:IMMP2L protein, human; D008666:Metalloendopeptidases; C068038:mitochondrial intermediate peptidase