Bathe, OliverHassanvand Jamadi, Robab2025-01-292025-01-292025-01-13Hassanvand Jamadi, R. (2025). Body composition features associated with renal cell carcinoma: exploring molecular mechanisms (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.https://hdl.handle.net/1880/120537Background: Renal cell carcinoma (RCC) is the most common form of kidney cancer, with clear cell RCC (ccRCC) being the most prevalent and aggressive subtype. This study seeks to identify body composition features visible on CT scans that are prognostic for ccRCC patients. In addition, I sought to determine if molecular features within the tumor are associated with one feature, sarcopenia. It is known that the clinical and molecular features of ccRCC are distinct in males and females. Therefore, I sought to identify sex-specific clinical and molecular features. Methods: Data from 538 patients with ccRCC were obtained from The Cancer Genome Atlas (TCGA) KIRC (Kidney renal clear cell carcinoma) cohort. Preoperative CT scans were available from The Cancer Imaging Archive (TCIA) for 200 patients. CT images at L3 were analyzed using Slice-O-Matic software to measure muscularity, fat distribution, muscle radiodensity, and fat radiodensity. Prognostic body composition features and clinical factors were identified in a multivariate manner. Subsequently, transcriptomic features in the tumor that were associated with low preoperative muscularity were identified in each sex. Gene set enrichment analysis (GSEA) was used to explore biological processes perturbed in ccRCC associated with sarcopenia. Results: Following a multivariate analysis, clinical stage, high subcutaneous fat density, and sarcopenia were found to be significantly associated with worse survival. Differentially expressed genes (DEGs) were compared in patients with low muscularity (sarcopenia) and high muscularity; the genes were different in males and females. Since sarcopenia was associated with T stage and M stage, DEGs that were also associated with advanced T- and M-stage were removed from the gene list, and only genes that were significantly correlated with skeletal muscle area (SMA) were kept in the final gene list. The final list of sarcopenia-associated DEGs consisted of 78 genes in males and 19 genes in females. GSEA demonstrated positive enrichment of pathways associated with proliferation. Interestingly, oxidative phosphorylation was negatively enriched in males and positively enriched in females, and the epithelial-mesenchymal transition was positively enriched in males and negatively enriched in females. The transcriptomic pattern of the sarcopenia-associated variant (SAV) of ccRCC was confirmed to be associated with a poor prognosis in validation cohorts. In addition, several of the gene sets were found to be enriched in the same manner in a small validation cohort. Conclusion: This thesis provides a comprehensive evaluation of the relationships of various body composition features measurable by CT scan, and overall survival. In addition, sex-specific transcriptomic and biological features of ccRCC associated with sarcopenia were identified.enUniversity 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.Renal Cell CarcinomaBody CompositionPrognosisSurvivalSarcopeniaMyosteatosisHigh Subcutaneous Fat RadiodensityCT Scan ImageSexual DimorphismTranscriptomeGenomicsGene ExpressionTranslational AnalysisClinicalBiophysics--MedicalOncologyEducation--SciencesPsychology--Clinicalmaster thesis