Impact of energy metabolism, paraoxonase-1, and inflammation on cancer patient’s prognosis and response to treatment

Abstract

Cancer is a worldwide health concern and a big challenge to increase the expectancy and quality of life. Considering that energy balance-related metabolism, OXS, and inflammation are key processes in cancer development and progression, the present thesis includes different human cohorts of patients with lung, head and neck, rectal, and breast cancer 1) to investigate the circulatory metabolic changes in cancer patients and the effects of oncological treatments produced on these metabolic alterations, and 2) to find potential biomarkers related to prognosis and response to treatment. Our results showed that patients with different types of cancer had several circulatory alterations in the concentrations of the energy-balance metabolites, PON1-related variables, and inflammatory parameters compared to controls. Some of these alterations were related to the clinicopathological characteristics of the patients. The administration of cancer treatments leads to a partial normalization of the circulatory levels of energy-balance metabolites showing similar metabolite concentrations from controls. Moreover, treatments were associated with an increase of PON1 concentration, and a further decrease of PON1 activities and inflammatory markers compared with pre-treatment values. Multivariate analyses and machine learning algorithms have provided relevant information about cancer metabolic alterations, as well as potential targets for cancer patients stratification according to their prognosis and response to treatment. However, further studies will be needed to confirm and validate the current findings.