11504 Background: There is a need for a reliable breast cancer biomarker that can predict a patient’s response to therapy. Serum glycans, or oligosaccharides, are of particular interest as over half of all proteins are glycosylated and alterations in glycosylation influence growth, adhesion, metastasis and immune surveillance of tumor, among other important functions. Serum glycans can be analyzed by high resolution mass spectrometry. Methods: Sera from patients with known metastatic breast cancer and age-matched healthy controls without medical problems were prospectively analyzed by mass spectroscopy. Women over the age of 18, who were not pregnant or breastfeeding, and who were without other active cancers were eligible. Samples were de-identified for laboratory personnel who analyzed sera by matrix-assisted laser desoprtion/ionization (MALDI) and Fourier transform ion-cyclotron resonance mass sepctrometry (FT ICR MS). Glycans were also profiled by chromatographic separation using a microchip nanoLC (Agilent) with a time-of-flight (TOF) mass analyzers. Results: Sera from 25 patients with metastatic breast cancer and 25 controls were evaluated. The mass profiles were obtained corresponding to both N-linked oligosaccharides (N-glycans) and O-linked oligosaccharides (O-glycans). Distinct variations in glycosylation were observed among sera analyzed from patients with metastatic breast cancer compared to controls. Specific glycan masses were analyzed and found to correspond to N-glycans. The chromatographic glycan profile showed individual glycans that were distinct for the cancer patients. Conclusions: Analysis of serum gylcans by mass spectrometry represents a new paradigm of cancer biomarker studies, focusing on post-translational modifications of proteins, rather than protein expression. Further refinement of this technology may be clinically useful in monitoring response to therapy in metastatic breast cancer. No significant financial relationships to disclose.
