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A cohort study investigating differences in skeletal muscle mitochondrial function between prostate cancer patients and healthy controls
Smart, Thomas Bass, Joseph Crossland, Hannah Cox, Jake Atherton, P Lund, Jonathan Phillips, Bethan
Smart, Thomas
Bass, Joseph
Crossland, Hannah
Cox, Jake
Atherton, P
Lund, Jonathan
Phillips, Bethan
Abstract
BACKGROUND: There has been an increasing prevalence of prostate cancer worldwide, and therefore a growing clinical need to understand and maintain whole body health in this cohort. There is currently limited evidence of the underlying physiology which leads to certain patients developing cancer cachexia. Based on pre-clinical evidence, skeletal muscle (SKM) mitochondria are suspected to play an integral role, however to date, there is little human data to support this. This study compares SKM mitochondrial oxidative phosphorylation (OXPHOS) in prostate cancer patients due to undergo treatment with curative intent to healthy volunteers, with a hypothesis that this would be lower in the cancer cohort. METHODS: Twelve prostate cancer patients and 8 disease-free males matched for age and body mass index (BMI) were recruited to this study. All participants completed assessments of physical function using clinically recognised tools (handgrip strength, timed up-and-go, and short physical performace battery) and muscle architecture via ultrasound. All participants also had a SKM (vastus lateralis) biopsy collected. Using a high-resolution respirometer (OROBOROS) and standardised substrate uncoupled inhibitor titration (SUIT) protocol, SKM OXPHOS was assessed, with the biopsy also analysed for citrate synthase activity and gene expression via RT-PCR. RESULTS: Despite our groups being well-matched in terms of age and BMI, and there being no differences in SKM physical function or architecture, extrinsic OXPHOS was significantly lower in the prostate cancer cohort compared to healthy controls (maximal complex I activity: 47.1 ± 19.7 vs. 27.1 ± 12.1, p = 0.01; maximal complex I + II activity: 74.8 ± 26.7 vs. 50.7 ± 13.4, p = 0.01; maximal activity: healthy: 95.9 ± 37.4 vs. 62.1 ± 16.3, p = 0.02). The same was true for Respiratory Control Ratio (2.7 ± 0.9 vs. 1.8 ± 0.9, p = 0.04). There was no difference in intrinsic OXPHOS between the groups. CONCLUSION: This study found lower SKM extrinsic OXPHOS in those with prostate cancer, in the absence of muscle mass or functional loss, when compared to age-matched disease-free volunteers. This appears to be due to changes in mitochondrial content or remodelling, with preservation of intrinsic function.
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Affiliations
University of Nottingham, University Hospitals of Derby and Burton NHS Foundation Trust
Date
2026-05-21
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Article
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Citation
Smart T.F., Bass J.J.,Crossland H. et al. A cohort study investigating differences in skeletal muscle mitochondrial function between prostate cancer patients and healthy controls. BMC Cancer (2026). https://doi.org/10.1186/s12885-026-16164-2
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© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.