RESUMO
OBJECTIVE: Breast cancer is a mortal disease that causes many deaths, especially in women. Improved therapies could contribute positively to survival rates. Metabolomics is an important tool for monitoring the alterations of several metabolites in clinical cases. This study aimed to develop a metabolomics model to observe (via mass spectroscopy) metabolic alterations in patients who suffered from breast cancer (BC), both before and after their recovery. MATERIALS AND METHODS: Grades 1 and 2 invasive ductal carcinoma patients were evaluated based on their positron emission tomography/computed tomography results. Fourteen patients who had fully recovered from BC were subjected to metabolomics analysis. Plasma samples were extracted and analyzed via quadrupole time-of-flight mass tandem spectroscopy. A chemometrics analysis was performed in order to determine the statistically significant metabolites. All the metabolites were annotated via the mummichog algorithm. RESULTS AND DISCUSSION: According to the data analysis, glucose, ornithine, phenyalanine, some vitamins, and metabolites in the fatty acid metabolism were statistically altered after recovery of each patient. CONCLUSION: Untargeted metabolomics studies can be used to understand the etiopathogenesis of breast cancer, finding new biomarkers and alterations of metabolic pathways. After the tumor burden was removed, homeostasis was restored and the concentration of several metabolites began to normalize. This study elucidated the effects of breast cancer at the molecular level.
Assuntos
Neoplasias da Mama , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Feminino , Neoplasias da Mama/patologia , Metaboloma , Metabolômica/métodos , BiomarcadoresRESUMO
Abstract Changes in metabolite levels of patients using the long-term drug can be comprehensively demonstrated by pharmacometabolomic studies. In this study, biological alterations induced by the administration of solifenacin succinate were investigated with a pharmacometabolomics approach on rat metabolism. Plasma samples obtained from rats were analyzed by LC-Q- TOF/MS/MS. METLIN and HMDB databases were used to identify metabolites. Data were processed and classified with MATLAB 2017b. 53 m/z values were found to be significantly different between the drug and control groups (p ≤ 0.01 and fold analysis > 1.5) and identified by comparing METLIN and HMDB databases. According to multivariate data analysis, changes in arachidonic acid, thromboxane A2, palmitic acid, choline, calcitriol, histamine phosphate, retinyl ester, l-cysteine, l-leucine, beta-alanine, l-histidine levels were found to be statistically significant compare to the control group. Differences in the biosynthesis of phenylalanine, aminoacyl-tRNA, tyrosine, tryptophan, metabolism of glycerophospholipid, cysteine, methionine, histidine, arachidonic metabolism have been successfully demonstrated by the metabolomics approach. Our study provides important information to explain the efficacy and toxicity of chronic administration of solifenacin succinate