Vogel, Hans J.Hyndman, Matthew EricFalegan, Oluyemi Seuntitun2019-09-232019-09-232019-09-12Falegan, O. S. (2019). Metabolomics and Metallomics Analyses of Renal Cell Carcinoma and Prostate Cancer (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.http://hdl.handle.net/1880/111036Prostate cancer and renal cell carcinoma of the kidney are the most frequently diagnosed and the most lethal male genitourinary cancers respectively. While prostate cancer screening and diagnosis using serum prostate-specific-antigen is flawed by its low sensitivity and inability to detect indolent disease, the histological diversity of renal cell carcinoma poses a clinical challenge for its identification in asymptomatic individuals. It is believed that applying new technologies such as metabolomics to the discovery of potential diagnostic and prognostic biomarkers, can enhance early detection of these cancers and improve overall patient survival while preserving a high quality of life. Considering this, the metabolome of biofluids associated with renal cell carcinoma and prostate cancer were analyzed and studied. Briefly, nuclear magnetic resonance spectroscopy and gas chromatography mass spectrometry techniques were used to analyze serum and urine samples obtained from renal cell carcinoma patients for isolating disease-specific metabolic profiles. Increased levels of lactate and pyruvate accompanied by reduced levels of specific tricarboxylic acid cycle metabolites were associated with renal cell carcinoma. Furthermore, benign oncocytomas of the kidney showed a differential metabolic profile from chromophobe renal cell carcinoma, with glycine and carnitine compounds at the center of the metabolic distinction. Our results showed that the prevalence of the Warburg effect, amino acid dysregulation and glutamine metabolism may distinguish renal cell carcinoma from benign renal lesions and thus presents a platform for identifying renal neoplastic transformations in asymptomatic individuals. On the other hand, the metabolome of seminal plasma measured by nuclear magnetic resonance spectroscopy distinguished prostate cancer Gleason grade 6 from 7, specifically increased lysine levels and reduced serine levels were significantly associated with low risk Gleason grade 6 disease. Also, the plasma and urinary metabolic pattern implicated amino acid dysregulation in bone metastasis of prostate tumors compared to low and high-risk disease. Our findings showed great potential for discriminating indolent from more aggressive prostate cancer, using a non-invasive method. Finally, our metallomics results indicate that metal ions may play a vital role in kidney cancer.engUniversity 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.metabolomicscancerprostate cancerrenal cell carcinomametallomicsBiochemistrydoctoral thesis10.11575/PRISM/37098