PROGNOSTIC SIGNIFICANCE OF SERUM INSULIN-LIKE GROWTH FACTORS (IGF) AND IGF-BINDING PROTEINS LEVELS IN BONE SARCOMA PATIENTS

DOI: https://doi.org/None

N.E. Kushlinskii, Yu.S. Timofeev, I.V. Boulytcheva, E.S. Gershtein, I.V. Babkina, I.N. Kuznetsov, Yu.N. Soloviev, M.D. Aliev N.N. Blokhin Russian Cancer Research Center, Kashirskoe shosse, 24, Moscow, Russian Federation, 115478

Introduction. Insulin-like growth factors (IGF) signaling system plays a major role in the development and progression of various sarcomas and other solid tumors, and therefore its components are regarded as promising diagnostic and prognostic tumor markers and targets for molecular- oriented therapy. Aim of the study. Evaluation of the prognostic significance of basal IGF-I, IGF-II and IGF-binding proteins (IGFBP) serum levels in patients with various malignant bone tumors. Materials and Methods. 25 osteosarcoma, 21 chondrosarcoma and 18 Ewing sarcoma patients with known pretreatment IGF-I, II, and type 1 and 3 IGFBPs serum levels measured with DSL Inc. (USA) ELISA kits were followed up for 15–61 (median – 35) months. Results. Increased IGF-I levels (>243 ng/ml) were associated with low relapse-free survival (RFS) in all bone sarcoma patients, and in those with chondrosarcoma. Overall survival (OS) depends in IGF-I level only in the total group. Patients with serum IGF-II exceeding 1.97 μg/ml also had RFS prognosis less favorable than those with lower levels of this marker. This association was most pronounced in Ewing sarcoma patients. IFGII level affected also OS indices in osteosarcoma cases. The s ignificant RFS and OS decrease was found at high (>31 ng/ml) IGFBP-1 serum levels in the total group, osteosarcoma and Ewing sarcoma patients. And IGFBP-3 level >5,85 μg/ml was associated with worse RFS in osteosarcoma, and decreased OS both in the total group, and in osteosarcoma and Ewing sarcoma patients. Conclusion. Unfavorable prognostic significance of high serum IGFs and IGFBPs concentrations both in the total group of bone sarcoma patients, and in various histological types of bone tumors was demonstrated. The value of individual IGF system components may change depending on the tumor histological type.
Keywords: 
IGF-I, IGF-II, IGFBP-1, IGFBP-3, osteosarcoma, chondrosarcoma, Ewing sarcoma, prognosis
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