吲哚胺2,3-双加氧酶和叉状头转录因子3在骨肉瘤中表达与预后的关系

Abstract

Objective To investigate the expression of indoleamine 2, 3-dioxygenase (IDO) and forkhead box P3(FOXP3) in the osteosarcoma, and evaluate the correlation between the expressions of IDO and FOXP3 protein and prognosis. Methods Cancer tissue samples were obtained from the patients (39 cases of osteosarcoma, 20 cases of giant cell tumor, 20 cases of osteochondroma) who were pathological diagnosed between May 2005 and September 2014 at the Second People Hospital of Shenzhen in China. Cancer tissue samples of osteosarcoma were obtained from postoperative tissue, giant cell tumor(GCT) tissue was obtained from the patients extremities with GCT, osteochondroma tissue was obtained from the patients extremities with osteochondroma; multiple lesions and hereditary multiple exostoses were excluded. The expressions of IDO and FOXP3 in osteosarcoma, osteochondroma and giant cell tumor tissues were studied by immunohistochemical staining. The statistical analysis was performed by using SPSS 19.0 software. Chi-square was used to analyze association between clinical parameters with IDO, FOXP3 expression subgroups. Kaplan-Meier and log-rank test were used for survival analysis. Cox analysis was performed to estimate univariate and multivariate analysis. Results IDO was expressed in 69.2% (27/39) and FOXP3 was expressed in 53.8% (21/39) of osteosarcoma. IDO was expressed in 15.0% (3/20) of giant cell tumor, but positive expression of FOXP3 was not found in giant cell tumor. Neither of them were found in osteochondroma, there were significant differences among the three groups in IDO and FOXP3 expressions(IDO: χ2=6.201, P<0.05; FOXP3: χ2=5.834, P<0.05). High expression of IDO (score≥5) was correlated with aggressive clinicopathologic features, such as lung metastasis, high surgical stage (Enneking stage)(χ2=6.594, P<0.05; χ2=8.770, P<0.05). Kaplan Meier-survival analysis showed that high expressions of IDO and FOXP3 were significantly associated with poor overall survival rates(χ2=8.905, P<0.05; χ2=4.573, P<0.05). Single factor variance analysis of overall survival rate showed that lung metastasis and high expression of IDO and FOXP3 were predicative factors of poor prognosis. However, only the lung metastasis was found to be an independent prognostic factor in multivariate analysis (HR=6.053, 95% CI: 13-34, P=0.040). There was no significant correlation between high the expression of IDO, FOXP3 and overall survival in multivariate analysis. Conclusion The expression of IDO, FOXP3 shows significant difference between benign and malignant tumors; thus high expression of IDO and FOXP3 is likely to be an effective predicative factor of poor prognosis for patients with osteosarcoma. Key words: Osteosarcoma; Immunohistochemistry; Indoleamine-pyrrole 2, 3, -dioxygenase; Forkhead transcription factors