Muscle Abnormalities in cancer patients: Exploring the biological characteristics of skeletal muscle of cancer patients

• Author / Creator

  Amritpal Singh Bhullar

• Computed tomography-derived muscle measures of sarcopenia and low muscle radiodensity have been associated with poor outcomes in cancer patients, however, the biological characteristics of the muscle in this population are not well understood. This research was conducted to first evaluate muscle measures of fiber size, fiber type, fat content and differentially expressed genes in males and female cancer patients. Secondly, the association between muscle radiodensity and fat content and distribution in rectus abdominis of cancer patients was determined. Lastly, the prognostic significance of biological features of skeletal muscle of cancer patients was assessed. To determine the biological features of muscle of cancer patients, rectus abdominis biopsies were collected from cancer patients undergoing open abdominal surgery scheduled as part of their clinical care. Clinical features, patient demographics, CT-derived muscle features, morphological features and muscle gene expression data of a large sample size provides a point of reference for these measures in the literature which are poorly described to date given published poor quality studies that commonly are characterized by sampling bias, discrepancies between sample collection and processing techniques, and failure to acknowledge factors that influence muscle biology. In our patient cohort (n=190), sexual dimorphism was evident in CT-derived muscle features and genes associated with muscle catabolism/anabolism. In the second study, it was hypothesized and also demonstrated that a negative association exists between muscle radiodensity and muscle triglyceride content [r = -0.409, p< 0.001 (N=75)]. Also, wide variation in muscle radiodensity was observed across the rectus abdominis (coefficient of variance = 3 to 61%). This is an important finding since, in the literature, a single abdominal CT image is used to define muscle radiodensity and then used to compare with biological features of the muscle. Also, the heterogeneous distribution of lipids in muscle compartments was observed suggesting that different and potentially multiple mechanisms contribute to fat infiltration in muscle. Prognostic significance of fatty acid composition of skeletal muscle phospholipids was determined (n=35), to reveal that depletion of arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in muscle phospholipids are risk factors for death in cancer patients [(HR, 0.29, 95%CI, 0.09-0.9), (HR, 0.23, 95%CI, 0.06-0.81) and (HR 0.23, 95%CI, 0.06 to 0.83), respectively]. Significantly lower content of ARA and a trend of lower EPA and DHA in skeletal muscle phospholipids were observed in patients who died within one year of surgery compared to who lived longer. It is concluded that there is a wide variation in the distribution of fat across the muscle and low muscle radiodensity might not be only because of fatty infiltrations. Other factors contributing to the radiodensity of muscle need to be explored. Also, the skeletal muscle phospholipid composition data we assembled suggests that alterations in membrane fatty acids can be prognostic in cancer patients. Further studies are required to confirm if the changes in fatty acid composition are systemic or selective and to explore the mechanisms involved.

• Subjects / Keywords

  • myosteatosis
  • Computed tomography
  • Muscle
  • Cancer
  • Radiodensity
  • membrane fatty acids

• Graduation date

  Fall 2019

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-q57d-5h21

• License

  Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.