Transferrin-bound proteins as potential biomarkers for advanced breast cancer patients

• Transferrin was found to interact with many candidate biomarkers.
• 21 significant proteins were identified bound to Transferrin.
• Many of these proteins are associated with the complement and coagulations systems.
• Fibrinogen and Fibronectin were found to have significant AUC values.
• High abundant proteins harbour potential diagnostic molecules.

BackgroundSerum profiling using mass spectrometry-based proteomic techniques has great potential to detect biomarkers that might improve the management for advanced breast cancer patients. The albuminome has previously been investigated as a tool in biomarker discovery, however other high abundant blood proteins are also likely to sequester potentially interesting molecules.MethodsAffinity resin purified and isolated Transferrin and associated bound proteins from normal control and breast cancer patient serum samples were analysed by label-free mass spectrometry during the discovery phase.Results21 significant proteins were identified with Fibrinogen and Fibronectin selected for further analysis in an independent sample set, with significant difference found when comparing the controls groups (normal healthy control, inflammatory bowel disease and benign breast disease) to stage IV breast cancer.ConclusionsThe area under the curve value for Fibrinogen compared favourably with cancer antigen 15-3, an established breast cancer tumour marker. A combination of all three biomarkers improved accuracy when comparing control/benign to stage IV breast cancer patient groups.General significanceMass spectrometry profiling of Transferrin-bound proteins has revealed serum proteins that can distinguish between serum from advanced breast cancer patients and healthy control subjects with high confidence.