Differential expression of genes related to mitochondrial biogenesis and bioenergetics in fatigued prostate cancer men receiving external beam radiation therapy.
OBJECTIVE
This prospective study explored relationships between expression changes of genes related to mitochondrial biogenesis/bioenergetics and fatigue in men with prostate cancer receiving external beam radiation therapy (EBRT).


METHODS
Fatigue and gene expression were measured before (Day 0), at midpoint (Days 19-21), and at completion (Days 38-42) of EBRT using the seven-item Patient-Reported Outcomes Measurement Information System-Fatigue short form and from whole blood cell RNA, respectively. The human mitochondria RT2 Profiler PCR Array System was used to identify differential expression of mitochondrial biogenesis/bioenergetics-related genes. Mixed linear modeling estimated the changes in fatigue and gene expression over time and determined significant associations between gene expression and fatigue.


RESULTS
Subjects were 50 men with prostate cancer (scheduled for EBRT = 25, active surveillance as matched controls = 25). The mean Patient-Reported Outcomes Measurement Information System-Fatigue T-score (mean = 50 ± 10 in a general population) for study subjects was 44.87 ± 5.89 and for controls was 43.5 ± 2.8 at baseline. Differential expression of two genes inside the mitochondria involved in critical mitochondrial complexes: BCS1L (β = 1.30), SLC25A37 (β = -2.44), and two genes on the outer mitochondrial membrane vital for mitochondrial integrity: BCL2L1 (β = -1.68) and FIS1 (β = -2.35) were significantly associated with changes in fatigue scores of study subjects during EBRT.


CONCLUSIONS
Genes related to oxidative phosphorylation, energy production, and mitochondrial membrane integrity are associated with worsening fatigue during EBRT. Further investigation of the pathways involved with this association may explain mechanisms behind the development of fatigue in this population.
National Institute of Nursing Research, National Institutes of Health, Bethesda, Maryland, USA; Case Western Reserve University, Cleveland, Ohio, USA. Electronic address: cxh416@case.edu.
Chao-Pin
CP
Hsiao
National Institute of Nursing Research, National Institutes of Health, Bethesda, Maryland, USA.
Dan
D
Wang
National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Aradhana
A
Kaushal
University of Arizona, Tucson, Arizona, USA.
Mei-Kuang
MK
Chen
National Institute of Nursing Research, National Institutes of Health, Bethesda, Maryland, USA.
Leorey
L
Saligan
D000074183:ATPases Associated with Diverse Cellular Activities; D000368:Aged; D000369:Aged, 80 and over; D027682:Cation Transport Proteins / Q000097:blood; D014450:Electron Transport Complex III / Q000097:blood; D004734:Energy Metabolism / Q000502:physiology / Q000528:radiation effects; D005221:Fatigue / Q000503:physiopathology*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism* / Q000528:radiation effects; D024101:Mitochondrial Proteins / Q000097:blood; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000503:physiopathology* / Q000532:radiotherapy*; D012720:Severity of Illness Index; D051020:bcl-X Protein / Q000097:blood
C494811:BCL2L1 protein, human; C435491:BCS1L protein, human; D027682:Cation Transport Proteins; C476525:FIS1 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C561492:Slc25a37 protein, human; D051020:bcl-X Protein; D000074183:ATPases Associated with Diverse Cellular Activities; D014450:Electron Transport Complex III
Fatigue; bioenergetics; biogenesis; gene expression; mitochondria; prostate cancer; radiation therapy