Body Composition Features in Colorectal Cancer: Clinical Outcomes and Biological Factors

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dc.contributor.advisorBathe, Oliver Frank
dc.contributor.authorArmstrong, Victoria Suzanne
dc.contributor.committeememberMacLean, Anthony
dc.contributor.committeememberBeck, Paul
dc.contributor.committeememberCulos-Reed, Nicole
dc.date2023-02
dc.date.accessioned2022-12-13T16:00:50Z
dc.date.available2022-12-13T16:00:50Z
dc.date.issued2022-12-06
dc.description.abstractBackground: 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.en_US
dc.identifier.citationArmstrong, 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.en_US
dc.identifier.urihttp://hdl.handle.net/1880/115581
dc.identifier.urihttps://dx.doi.org/10.11575/PRISM/40521
dc.language.isoengen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectColorectal canceren_US
dc.subjectCachexiaen_US
dc.subjectMuscle wastingen_US
dc.subjectAdipose tissue wastingen_US
dc.subjectBody composition featuresen_US
dc.subjectSurvival outcomesen_US
dc.subject.classificationEducation--Sciencesen_US
dc.subject.classificationBioinformaticsen_US
dc.subject.classificationBiostatisticsen_US
dc.subject.classificationPhysiologyen_US
dc.subject.classificationBiophysics--Medicalen_US
dc.subject.classificationOncologyen_US
dc.titleBody Composition Features in Colorectal Cancer: Clinical Outcomes and Biological Factorsen_US
dc.typemaster thesisen_US
thesis.degree.disciplineMedicine – Medical Sciencesen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameMaster of Science (MSc)en_US
ucalgary.item.requestcopytrueen_US
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