RESUMEN
This study was targeted on a metabolomic approach to compare the blood serum free amino acid profiles and concentration of confirmed breast cancer (stages I-III) patients to healthy controls in order to establish reliable biomarkers of early detection and prediction of breast cancer. The ultra-high-performance liquid chromatography coupled with mass spectrometry using positive ionization electrospray was applied for the picoline-derivatized serum free amino acids using the EZ:faastTM kit. Multivariate statistical analysis principal component analysis, partial least squares discrimination analysis and univariate analysis were applied in order to discriminate between patient groups and putative amino acid biomarkers for breast cancer. A significant decrease of amino acid concentrations between the breast cancer group and the control group was positively correlated with breast cancer progression. Arginine, Alanine, Isoleucine, Tyrosine and Tryptophan were identified as being good potential discriminants (AUROC ≥0.85) and suitable candidates to diagnose and predict the breast cancer progression.
Asunto(s)
Aminoácidos/sangre , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/diagnóstico , Detección Precoz del Cáncer/métodos , Metaboloma , Adulto , Anciano , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión/métodos , Progresión de la Enfermedad , Femenino , Humanos , Metabolómica/métodos , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Picolinas/química , Análisis de Componente Principal , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
SERS analysis of biofluids, coupled with classification algorithms, has recently emerged as a candidate for point-of-care medical diagnosis. Nonetheless, despite the impressive results reported in the literature, there are still gaps in our knowledge of the biochemical information provided by the SERS analysis of biofluids. Therefore, by a critical assignment of the SERS bands, our work aims to provide a systematic analysis of the molecular information that can be achieved from the SERS analysis of serum and urine obtained from breast cancer patients and controls. Further, we compared the relative performance of five different machine learning algorithms for breast cancer and control samples classification based on the serum and urine SERS datasets, and found comparable classification accuracies in the range of 61-89%. This result is not surprising since both biofluids show striking similarities in their SERS spectra providing similar metabolic information, related to purine metabolites. Lastly, by carefully comparing the two datasets (i.e., serum and urine) we show that it is possible to link the misclassified samples to specific metabolic imbalances, such as carotenoid levels, or variations in the creatinine concentration.