Untargeted Urinary 1H NMR-Based Metabolomic Pattern as a Potential Platform in Breast Cancer Detection.
Catarina Luís SilvaAna OlivalRosa PerestreloPedro SilvaHelena TomásJosé S CâmaraPublished in: Metabolites (2019)
Breast cancer (BC) remains the second leading cause of death among women worldwide. An emerging approach based on the identification of endogenous metabolites (EMs) and the establishment of the metabolomic fingerprint of biological fluids constitutes a new frontier in medical diagnostics and a promising strategy to differentiate cancer patients from healthy individuals. In this work we aimed to establish the urinary metabolomic patterns from 40 BC patients and 38 healthy controls (CTL) using proton nuclear magnetic resonance spectroscopy (1H-NMR) as a powerful approach to identify a set of BC-specific metabolites which might be employed in the diagnosis of BC. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was applied to a 1H-NMR processed data matrix. Metabolomic patterns distinguished BC from CTL urine samples, suggesting a unique metabolite profile for each investigated group. A total of 10 metabolites exhibited the highest contribution towards discriminating BC patients from healthy controls (variable importance in projection (VIP) >1, p < 0.05). The discrimination efficiency and accuracy of the urinary EMs were ascertained by receiver operating characteristic curve (ROC) analysis that allowed the identification of some metabolites with the highest sensitivities and specificities to discriminate BC patients from healthy controls (e.g. creatine, glycine, trimethylamine N-oxide, and serine). The metabolomic pathway analysis indicated several metabolism pathway disruptions, including amino acid and carbohydrate metabolisms, in BC patients, namely, glycine and butanoate metabolisms. The obtained results support the high throughput potential of NMR-based urinary metabolomics patterns in discriminating BC patients from CTL. Further investigations could unravel novel mechanistic insights into disease pathophysiology, monitor disease recurrence, and predict patient response towards therapy.
Keyphrases
- end stage renal disease
- newly diagnosed
- ejection fraction
- high throughput
- chronic kidney disease
- magnetic resonance
- stem cells
- computed tomography
- ms ms
- healthcare
- amino acid
- young adults
- bone marrow
- type diabetes
- mesenchymal stem cells
- skeletal muscle
- electronic health record
- machine learning
- insulin resistance
- big data
- case report
- gas chromatography mass spectrometry
- protein kinase