Body Composition Features in Colorectal Cancer: Clinical Outcomes and Biological Factors
Date
2022-12-06
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Abstract
Background: Cancer is a global health burden and a leading cause of death worldwide. One obstacle to improving patient outcomes is the development of cancer cachexia, which is formally described as the loss of muscle tissue (with or without adipose tissue atrophy). The classical presentation of cachexia is low muscle mass (sarcopenia) which can be assessed by computed tomography (CT) image assessment techniques, but this may not embody all important body composition phenotypes. I hypothesize that cancer can induce multiple clinically significant body composition (BC) features beyond sarcopenia, such as myosteatosis and high subcutaneous fat density (dense sub-q). Methods: In a cohort of patients with stage I – IV colorectal cancer (CRC) (N = 319), BC features were measured using Slice-O-Matic CT image analysis techniques. The influence of BC phenotypes and other clinical parameters on overall survival (OS) outcomes was assessed using univariate Kaplan-Meier and multivariate Cox regression analyses. Findings were then validated on an external dataset of 960 patients with CRC. To explore the physiological basis of these BC features, I performed targeted serum proteomics using Luminex assays and untargeted shotgun tumor proteomics using liquid chromatography-mass spectrometry. Results: Overall, the three BC features (sarcopenia, myosteatosis and dense sub-q) appeared independent of one another in 60% of cases. Myosteatosis and dense sub-q were independent predictors of worse OS outcomes (P < 0.001, P = 0.050). Sarcopenia was influential on reducing OS when phenotypic overlap was removed (P = 0.002). Several perturbed protein correlates were found in relation to each BC phenotype, specifically with respect to inflammation and metabolic processes. For example, myosteatosis was independently associated with increased leptin, resistin and adipsin (P < 0.01 for all). Conclusion: Overall, this work demonstrates that colorectal cancer can lead to the development of several BC phenotypes beyond just muscle wasting. Distinct patterns of serum protein abundance suggested that each of the BC features represented biologically distinct manifestations.
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Keywords
Colorectal cancer, Cachexia, Muscle wasting, Adipose tissue wasting, Body composition features, Survival outcomes
Citation
Armstrong, V. S. (2022). Body composition features in colorectal cancer: clinical outcomes and biological factors (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.