Differential Expression of Genes Related to Mitochondrial Biogenesis and Bioenergetics in Fatigued Prostate Cancer Men Receiving External Beam Radiation Therapy

• Published in: Journal of pain and symptom management Vol. 48; no. 6; pp. 1080 - 1090
• Main Authors: Hsiao, Chao-Pin, Wang, Dan, Kaushal, Aradhana, Chen, Mei-Kuang, Saligan, Leorey
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.2014; Elsevier
• Subjects: Aged; Aged, 80 and over; Anesthesia; ATPases Associated with Diverse Cellular Activities; bcl-X Protein - blood; bioenergetics; biogenesis; Biological and medical sciences; Cation Transport Proteins - blood; Electron Transport Complex III - blood; Energy Metabolism - physiology; Energy Metabolism - radiation effects; Fatigue; Fatigue - physiopathology; gene expression; Gene Expression Profiling; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Membrane Proteins - blood; Middle Aged; mitochondria; Mitochondria - metabolism; Mitochondria - radiation effects; Mitochondrial Proteins - blood; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Nephrology. Urinary tract diseases; Pain Medicine; Pharmacology. Drug treatments; Prospective Studies; prostate cancer; Prostatic Neoplasms - physiopathology; Prostatic Neoplasms - radiotherapy; radiation therapy; Severity of Illness Index; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; prostate cancer; bioenergetics; mitochondria; radiation therapy; Fatigue; biogenesis; gene expression; Human; Urinary system disease; Prostate disease; Male; Malignant tumor; Gene expression; Radiotherapy; Extracorporeal irradiation; Mitochondria; Treatment; Adult; Male genital diseases; Prostate cancer; Cancer
• ISSN: 0885-3924; 1873-6513; 1873-6513
• DOI: 10.1016/j.jpainsymman.2014.03.010

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). 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. 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. 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.