Circulating Candidate Biomarkers in Giant Cell Tumors of Bone

• Published in: Proteomics. Clinical applications 2018-11, Vol.12 (6), p.e1800041-n/a
• Main Authors: Conti, Amalia, Luchini, Alessandra, Benassi, Maria Serena, Magagnoli, Giovanna, Pierini, Michela, Piccinni‐Leopardi, Martina, Quattrini, Irene, Pollino, Serena, Picci, Piero, Liotta, Lance A., Pazzaglia, Laura
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biomarkers; Biomarkers, Tumor - blood; Bone Neoplasms - blood; Bone Neoplasms - epidemiology; Bone Neoplasms - pathology; Bone tumors; Cell activation; Cluster analysis; Design of experiments; Experimental design; Female; Gene Expression Regulation, Neoplastic - genetics; Giant Cell Tumors - blood; Giant Cell Tumors - epidemiology; Giant Cell Tumors - pathology; GRB2 Adaptor Protein - blood; Grb2 protein; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; Hydrogels; Kinases; Low molecular weights; Lung Neoplasms - blood; Lung Neoplasms - pathology; Lung Neoplasms - secondary; Male; Metastases; Metastasis; Middle Aged; Molecular weight; Multivariate analysis; Nanoparticles; Nanoparticles - chemistry; Neoplasm Grading; Neoplasm Metastasis; Neoplastic Cells, Circulating; Patients; Prognosis; prognostic biomarkers; Protein Serine-Threonine Kinases - blood; Proteins; Proteome - classification; Proteome - genetics; Proteomes; Regulators; Risk Factors; Serum levels; Serum proteins; Signal transduction; STAT5 Transcription Factor - blood; Statistical analysis; Substrates; Tumors; Wound healing; Young Adult
• ISSN: 1862-8346; 1862-8354; 1862-8354
• DOI: 10.1002/prca.201800041

Purpose Approximately 5% of giant cell tumors (GCT) of bone develop pulmonary metastases. Although many biomarkers have been proposed, identification of circulating low abundance molecules may be useful to predict malignant progression. Experimental design The hydrogel nanoparticle technique followed by MS was used to detect low molecular weight serum proteins or protein fragments in serum of 20 GCT patients with different clinical course and in ten healthy sera used as control. The most representative low‐abundant de novo or differentially abundant proteins were submitted to String database that recognized interconnected activated pathways including protein activation cascade, wound healing, cell‐substrate adhesion, and response to stress. Statistics were performed for identification of candidate prognostic factors. Results Proteome cluster analysis separated metastasis‐free from metastatic GCT patients in two well‐defined groups where serum levels of signaling 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. Multivariate analysis demonstrated that tumor grade and STAT5B were independent prognostic factors. Conclusions and clinical relevance By using a noninvasive technique, we identified differentially abundant serum candidate biomarkers, also providing prognostic information in patients with GCT of bone.