High-performance metabolic marker assessment in breast cancer tissue by mass spectrometry
Autor: | Laura Cesaratto, Paola Picotti, Viviana Londero, Carla Cedolini, Gennaro Esposito, Alessandra Corazza, Chiara Zuiani, Massimo Bazzocchi, Carlo Pucillo, Elena Betto, Maria Chiara Mimmi |
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Rok vydání: | 2010 |
Předmět: |
Magnetic Resonance Spectroscopy
Metabolite Clinical Biochemistry Biopsy Fine-Needle Breast Neoplasms tumor marker detection by nuclear magnetic resonance and mass spectrometry Mass spectrometry Mass Spectrometry choline metabolites chemistry.chemical_compound breast cancer Breast cancer breast tissue metabonomics In vivo Biopsy medicine Biomarkers Tumor Choline Humans Phosphocholine Chromatography mass spectrometry metabonomics Biochemistry (medical) medicine.diagnostic_test General Medicine Reference Standards medicine.disease chemistry Ex vivo Chromatography Liquid |
Zdroj: | Clinical chemistry and laboratory medicine. 49(2) |
ISSN: | 1437-4331 |
Popis: | Background: The identification of reliable markers for diagnosis of breast cancer has been thoroughly addressed by metabolic profiling using nuclear magnetic resonance (NMR) spectroscopy or imaging. Several clear diagnostic indicators have emerged using either in vitro analysis of tissue extracts, ex vivo analysis of biopsies or in vivo direct spectral observations. Most of the breast cancer characteristic metabolites could be assayed by mass spectrometry (MS) to exploit the superior sensitivity of this technique and therefore reduce the traumatic impact of current biopsy procedures. Methods: Following extraction, aqueous metabolite mixtures were obtained that were submitted to liquid-chromatography, electrospray-ionization, mass spectrometry (LC/ESI-MS) analysis to estimate the content of choline (Cho) and its phosphorylated derivatives, phosphocholine (PCho) and glycerophosphocholine (GPCho). The determinations were performed using 10 samples from breast tissue biopsies, surgical specimens and one single sample of a hepatic metastasis. In addition, some measurements were also repeated using high-resolution 1H NMR spectroscopy to complement the mass spectrometry results. Results: The contents of Cho, PCho and GPCho in breast tissue extracts were estimated by LC/ESI-MS based on standard compound calibration curves. Sharply increased ratios of phosphorylated-to-unphosphorylated metabolites, PCho/ Cho and (PCho+GPCho)/Cho, were observed in all tumor samples, although without discrimination between benign and malignant lesions, contrary to samples from healthy individuals and from those with fibrocystic disease. Conclusions: The assessment of breast cancer markers by LC/ESI-MS is feasible and diagnostically valuable. In addition to high sensitivity, the approach also shows a resolution advantage for assaying choline derivatives compared to NMR, and could complement the latter. |
Databáze: | OpenAIRE |
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