Biomarker discovery using urinary metabolomics for noninvasive early cancer detection

The development of new screening methods for the early detection of cancer remains one of the foremost challenges facing modern cancer research. The emergence of new analytical technologies and their application to \u27omics\u27-based approaches has provided researchers with powerful new tools for molecular biomarker discovery that may benefit early screening of cancer. This dissertation outlines several key advances made toward the application of urinary metabolomics to cancer biomarker discovery. The term urinary metabolomics here refers to the investigation of small metabolites in urine as potential disease biomarkers. The advantage of using this approach lies in its noninvasive sampling characteristics and robust analytical feasibility. The dissertation begins with the development of two analytical methods for the determination of sarcosine in urine for the early detection of prostate cancer. The next three papers discuss the analytical challenges facing the determination of pteridine derivatives in biological samples and present a new method to adjust their levels to patient hydration status and time since last urination. Briefly, pteridines and their derivatives function as intermediates in the metabolism of various vitamins and cofactors, where altered levels of pteridines have been reported in the urine of patients with several types of epithelial cancers, among other diseases. The following paper explores the possibility of using urinary metals as potential cancer biomarkers in a proof-of-concept study. The final two papers investigate the biological variation of urinary pteridines in order to better understand how urinary metabolites naturally fluctuate, and apply this information to a new method for the comprehensive determination of pteridine derivatives in urine. Taken together, this body of research presents new opportunities and challenges in the discovery of new cancer biomarkers --Abstract, page iv