Metabolomics and bladder cancer : risk factors and prognosis of the most common cancer of the urinary tract

Bladder cancer is the sixth most common malignancy worldwide in males and is considered as a disease of the elderly, because its incidence increases steeply with age. It has a high recurrence rate and a high risk of progression to more invasive and potentially lethal forms. The current approach to assess the evolution of the disease is the use of cystoscopy, a painful invasive method that carries in many cases burdens in patients. The need to repeat these controls very often increases, in addition, the total cost of management of this disease, making bladder cancer one of the most expensive cancers for the health systems. For all this, there is an urgent need to find noninvasive markers that can predict the recurrence and progression of the disease. Significant advances have been made in the areas of genomics and transcriptomics, but there are still no metabolic markersthat could be conveniently evaluated in patients' urine, improving the predictive capacity of existing markers. During this thesis work, we have investigated the possibility of finding such markers in urine applying mass spectrometry and nuclear magnetic resonance. In addition, we have studied the metabolic mechanisms that cells with different degrees of risk of evolution use for their energy production. Finally, we have characterized the mechanism of action of a potentially effective drug against schistosomiasis, an infection that is at the base of the appearance of bladder cancer in endemic regions of Africa, Asia and South America. During this work I have contributed to the development of different methods of data collection and statistical analysis, as well as to the biochemical interpretation of the results. Our observations have opened new paths that could allow in the future a deeper understanding of the causes of risk, diagnosis and prognosis of this disease, that is already the most common cancer of the urinary system.