Abstract
BackgroundOsteosarcoma is a malignant bone tumor with a high potential for lung metastasis, and the prognosis for patients with metastatic disease is very poor. The interaction between fibronectin (FN) and integrin αvβ3 in soft-tissue sarcoma promotes cell migration, invasion, and lung metastasis. This study aimed to investigate the prognostic significance of FN and αvβ3 in osteosarcoma.MethodsImmunohistochemistry and western blotting were used to detect the expression of FN and αvβ3 in 60 osteosarcoma specimens and in 30 osteochondroma specimens. Furthermore, correlations of FN and αvβ3 with the clinicopathological features of osteosarcoma patients were analyzed using the χ2 test and Fisher’s exact test. Disease-free survival and overall survival of osteosarcoma patients were assessed using the Kaplan-Meier method and Cox proportional hazards model. The predictive accuracy of the model was determined by the Harrell concordance index.ResultsFN (P < 0.05) and αvβ3 (P < 0.05) were overexpressed in osteosarcoma specimens compared with osteochondroma specimens. High FN expression was associated with a poor response to chemotherapy (P = 0.001) and poor disease-free (P < 0.001) and overall (P < 0.001) survival. High expression of αvβ3 was linked to an advanced surgical stage (P = 0.028), a poor response to chemotherapy (P = 0.002), and both poor disease-free survival (P < 0.001) and overall survival (P < 0.001). FN and αvβ3 co-expression were associated with sex (P = 0.011), an advanced surgical stage (P = 0.013), and a poor response to chemotherapy (P = 0.002). Moreover, high expression of both proteins can serve as an independent prognostic value for reduced survival time in osteosarcoma patients.ConclusionsThe results of this study suggest that FN and αvβ3 expression is associated with an unfavorable clinical outcome of osteosarcoma, and these molecules may constitute attractive therapeutic targets for osteosarcoma treatment. To improve the survival of osteosarcoma patients, further investigations are required to clarify their prognostic values in a larger population.
Highlights
As the most frequently observed primary aggressive bone tumor, osteosarcoma occurs most often in childhood and adolescence, with a second incidence peak among individuals over 50 years of age [1]
FN and integrin αvβ3 were highly expressed in 19 (31.7%) and 16 (26.7%) of 60 osteosarcoma cases, which were not observed in the 30 osteochondroma cases
We found that high expression of FN or αvβ3 individually as well as their combined expression can serve as predictors for poor clinical survival among osteosarcoma patients
Summary
As the most frequently observed primary aggressive bone tumor, osteosarcoma occurs most often in childhood and adolescence, with a second incidence peak among individuals over 50 years of age [1]. Aggressive therapeutic modalities, including surgical resection and combinational chemotherapy, can cure 70% of patients with localized disease. The prognosis of patients with metastatic or relapsed osteosarcoma remains unfavorable, with no improvement over the past 30 years [1]. Further investigation of the biomarkers for the prognosis of osteosarcoma is needed to develop effective agents for treatment. Osteosarcoma is a malignant bone tumor with a high potential for lung metastasis, and the prognosis for patients with metastatic disease is very poor. This study aimed to investigate the prognostic significance of FN and αvβ in osteosarcoma
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