Assessment of IGF-۱ level in serum andIGF-۱R gene and protein levels in tumor tissues of patients with Ewing sarcoma

Background: Ewing sarcoma belongs to primary malignantbone tumors which is commonly identified by a specific chromosomalrearrangement and its subsequent encoded fused oncoprotein(EWS-FLI۱). Insulin-like growth factor-۱ (IGF-۱)and IGF-۱ receptor (IGF-۱R) are members of IGF axis whichare involved in different physiological processes and their rolehave been considered in a variety of pathological conditions.This study is aimed to illuminate the association of IGF-۱ andits receptor in Ewing sarcoma aggressiveness and deteriorationof patients.Materials and Methods: The total number of ۹۰ specimensincluding ۳۰ tumor tissues, ۳۰ healthy tissues and ۳۰ bloodsamples of patients with Ewing sarcoma were enrolled in thisstudy. ELISA was conducted to measure the circulating level ofIGF-۱ in serum samples. Additionally, in tumor tissue samplesand their adjacent normal margin, IGF-۱R gene and protein expressionwas assessed while using qRT-PCR and immunohistochemistry.Unpaired t-test and Mann-Whitney U test were usedto perform side-to-side comparison.Results: Ewing sarcoma patients demonstrated significantly anincreased level of circulating IGF-۱ in comparison with healthycontrols. Moreover, IGF-۱R gene and protein expression weresignificantly upregulated in tumor tissue samples compared tonon-cancerous margins. Also, the circulating and local expressionpattern of IGF-۱ and IGF-۱R at both gene and protein levelwere elevated in Ewing sarcoma patients with more severe conditions(patients with high grade tumor, chemotherapy positivestatus, metastasis and tumor recurrence). Notably, this increasementwas statistically significant in patients who had metastaticand recurrent tumors. Additionally, IGF-۱ upregulation wassignificant in cases with high grade tumors.Conclusion: Our data provide insights into the role of IGF-۱and IGF-۱R in pathogenesis of Ewing sarcoma. Although morestudies are needed to determine the exact molecular mechanismsand signaling pathways of these two ligand and receptor,they might serve as targets for more specific therapy of Ewingsarcoma.

کلیدواژه ها:

Ewing sarcoma ، Metastasis ، Malignancy ، IGF