Osteosarcoma (OS) and Ewing tumor (ET) together account for the majority of musculoskeletal sarcomas diagnosed in patients of all ages and nearly 90% of those occurring in children and adolescents. Natural IgM antibodies to tumor antigen have been reported in patients with early-stage cancer, and a panel of serum antibodies can detect cancer many years prior to imaging detection. Circulating immune complexes formed by tumor antigens and immunoglobulin M (IgM) represent a novel class of biomarkers with diagnostic value for early cancer detection. In the present study, we investigated the presence of ANG-IgM, VEGF-IgM, bFGF-IgM, PDGF-IgM in the sera of children with bone tumors. The study included 174 pediatric patients with newly diagnosed bone tumors. Express ELISA techniques have been developed to quantify immune complexes in INR. Serum samples from all patients were analyzed for the presence of biomarker-IgM immune complexes. We compared the serum level of angiogenic factors and immune complexes in children with different types of bone tumors. The highest concentration of VEGF-IgM was detected in ET patients and ANG-IgM in OS patients. The present study demonstrated increased ANG-IgM expression in the sera OS patients and a positive correlation between its expression levels and tumor vascularity evaluated by CTA. Our results have potential applications as biomarkers for controlling unwanted angiogenesis, early diagnosis and response to therapy in children with bone tumors.
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