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Relationships between expression of BCS1L, mitochondrial bioenergetics, and fatigue among patients with prostate cancer

Authors Hsiao CP, Chen MK, Veigl ML, Ellis R, Cooney M, Daly B, Hoppel C

Received 29 January 2019

Accepted for publication 7 May 2019

Published 18 July 2019 Volume 2019:11 Pages 6703—6717

DOI https://doi.org/10.2147/CMAR.S203317

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 3

Editor who approved publication: Professor Nakshatri


Chao-Pin Hsiao1,2, Mei-Kuang Chen,3 Martina L Veigl,4 Rodney Ellis,5 Matthew Cooney,6 Barbara Daly,1 Charles Hoppel7

1The Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, USA; 2School of Nursing, Taipei Medical University, Taipei , Taiwan; 3Department of Psychology, University of Arizona, Tucson, AZ, USA; 4Gene Expression & Genotyping Facility, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA; 5Department of Radiation Oncology and Urology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; 6Department of Medical Oncology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; 7Center for Mitochondrial Disease, Department of Pharmacology and Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA

Introduction: Cancer-related fatigue (CRF) is the most debilitating symptom with the greatest adverse side effect on quality of life. The etiology of this symptom is still not understood. The purpose of this study was to examine the relationship between mitochondrial gene expression, mitochondrial oxidative phosphorylation, electron transport chain complex activity, and fatigue in prostate cancer patients undergoing radiotherapy (XRT), compared to patients on active surveillance (AS).
Methods: The study used a matched case–control and repeated-measures research design. Fatigue was measured using the revised Piper Fatigue Scale from 52 patients with prostate cancer. Mitochondrial oxidative phosphorylation, electron-transport chain enzymatic activity, and BCS1L gene expression were determined using patients’ peripheral mononuclear cells. Data were collected at three time points and analyzed using repeated measures ANOVA.
Results: The fatigue score was significantly different over time between patients undergoing XRT and AS (P<0.05). Patients undergoing XRT experienced significantly increased fatigue at day 21 and day 42 of XRT (P<0.01). Downregulated mitochondrial gene (BC1, ubiquinol-cytochrome c reductase, synthesis-like, BCS1L, P<0.05) expression, decreased OXPHOS-complex III oxidation (P<0.05), and reduced activity of complex III were observed over time in patients with XRT. Moreover, increased fatigue was significantly associated with downregulated BCS1L and decreased complex III oxidation in patients undergoing XRT.
Conclusion: Our results suggest that BCS1L and complex III in mitochondrial mononuclear cells are potential biomarkers and feasible therapeutic targets for acute XRT-induced fatigue in this clinical population.

Keywords: BCS1L, gene expression, mitochondrial bioenergetics, cancer-related fatigue, prostate cancer, radiation therapy

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