Abstract

Identifying prognostic factors for osteosarcoma (OS) aids in the selection of patients who require more aggressive management. XB130 is a newly characterized adaptor protein that was reported to be to be a prognostic factor of certain tumor types. However, the association between XB130 expression and the prognosis of OS remains unknown. In the present study, we investigated the association between XB130 expression and clinicopathologic features and prognosis in patients suffering osteosarcoma, and further investigated its potential role on OS cells in vitro and vivo. A retrospective immunohistochemical study of XB130 was performed on archival formalin-fixed paraffin-embedded specimens from 60 pairs of osteosarcoma and noncancerous bone tissues, and compared the expression of XB130 with clinicopathological parameters. We then investigate the effect of XB130 silencing on invasion in vitro and lung metastasis in vivo of the human osteosarcoma cell line. Immunohistochemical assays revealed that XB130 expression in osteosarcoma tissues was significantly higher than that in corresponding noncancerous bone tissues (P=0.001). In addition, high XB130 expression more frequently occurred in osteosarcoma tissues with advanced clinical stage (P=0.002) and positive distant metastasis (P=0.001). Moreover, osteosarcoma patients with high XB130 expression had significantly shorter overall survival and disease-free survival (both P<0.001) when compared with patients with the low expression of XB130. The univariate analysis and multivariate analysis shown that high XB130 expression and distant metastasis were the independent poor prognostic factor. We showed that XB130 depletion by RNA interference inhibited invasion of XB130-rich U2OS cells in vitro and lung metastasis in vivo. This is the first study to reveal that XB130 overexpression may be related to the prediction of metastasis potency and poor prognosis for osteosarcoma patients, suggesting that XB130 may serve as a prognostic marker for the optimization of clinical treatments. Furthermore, XB130 is the potential molecular target for osteosarcoma therapy.

Keywords: Osteosarcoma; XB130; Immunohistochemistry; Prognosis; RNA interference