PO-485 Low abundance circulating proteins in giant cell tumours of bone

Abstract

IntroductionCirculating low-abundance proteins/fragments generating from tumour cells and tissues, represent the most important source of cancer biomarkers useful for early diagnosis and prognosis. Giant cell tumour of bone (GCT) is a benign neoplasm occurring in the long bone and in the axial skeleton of young adults. Approximately 5% of GCT develop pulmonary metastases. Although many biomarkers have been proposed, identification of circulating low abundance molecules may be useful to predict metastasis with a non invasive method.Material and methodsThe hydrogel nanoparticles technique followed by mass spectrometry was used to detect low molecular weight serum proteins or protein fragments in serum of 20 GCT patients with different clinical course and in 10 healthy sera used as control. The most representative low-abundant de novo or differentially abundant proteins were submitted to String database in order to define protein-protein interaction network. Cluster analysis was performed to identify prognostic groups of patients with similar abundance of proteins that significantly discriminate between the groups.Results and discussionsFor the 25 low-abundant de novo or differentially abundant proteins identified, we recognised that the top interconnected pathways included protein activation cascade, wound healing, blood coagulation, cell-substrate adhesion. Proteoma cluster analysis separated metastasis-free from metastatic GCT patients in two well-defined groups where serum levels of signalling transduction mediators and regulators of kinase activity presented a high discriminatory power. Increased expression of proteins STAT5B, GRB2 and OXSR1 was related to a higher probability of metastasis.ConclusionIn conclusion, using a no invasive technique, we identified differentially abundant serum biomarkers, also providing prognostic information in patients with GCT of bone. Future studies are ongoing to establish the interplay between these biomarkers in order to fully understand the mechanism involved in tumour development and to focus on the planning of tailored therapies that should be more effective and less toxic.