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Background <p>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.</p> Methods <p>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.</p> Results <p>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, <i>p</i> = 0.01; maximal complex I + II activity: 74.8 ± 26.7 vs. 50.7 ± 13.4, <i>p</i> = 0.01; maximal activity: healthy: 95.9 ± 37.4 vs. 62.1 ± 16.3, <i>p</i> = 0.02). The same was true for Respiratory Control Ratio (2.7 ± 0.9 vs. 1.8 ± 0.9, <i>p</i> = 0.04). There was no difference in intrinsic OXPHOS between the groups.</p> Conclusion <p>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.</p>

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A cohort study investigating differences in skeletal muscle mitochondrial function between prostate cancer patients and healthy controls

  • 期刊论文

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  • 发表日期：

    2026年5月21日

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  • Thomas FF Smart,
  • Joseph J Bass,
  • Hannah Crossland,
  • Jake Cox,
  • Philip J Atherton,
  • Jon N Lund,
  • Bethan E Phillips

摘要

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.