Prognostic value of microRNA-223/epithelial cell transforming sequence 2 signaling in patients with osteosarcoma.

Abstract

MicroRNA-223 (miR-223) has been demonstrated to be implicated in cell proliferation and cell cycle progression of osteosarcoma cell lines by regulating its target gene epithelial cell transforming sequence 2 (ECT2). However, the clinical significance of the deregulation of the miR-223/Ect2 axis in human osteosarcoma has not been fully elucidated. To address this problem, we firstly showed that the expression levels of miR-223 and Ect2 messenger RNA were, respectively, down-regulated and up-regulated in osteosarcoma tissues compared with those in noncancerous bone tissues significantly (both P < .001), according to the results of quantitative real-time reverse transcription-polymerase chain reaction. Notably, miR-223 down-regulation was negatively correlated with Ect2 messenger RNA up-regulation in osteosarcoma tissues (r = -0.68, P = .01). Then, the combined low miR-223 expression and high Ect2 expression (miR-223-low/Ect2-high) was significantly associated with high tumor grade (P = .01), poor response to chemotherapy (P = .01), positive metastasis (P < .001), and recurrence (P < .001) of osteosarcomas. Moreover, patients with miR-223-low/Ect2-high expression had the shortest overall survival (P < .001) and disease-free survival (P < .001) compared with patients in the other 3 groups (miR-223-low/Ect2-low, miR-223-high/Ect2-high, and miR-223-high/Ect2-low). Furthermore, the multivariate analysis identified miR-223/Ect2 expression and the status of metastasis as independent prognostic factors for overall survival and disease-free survival. In conclusion, our data offer convincing evidence that the deregulation of miR-223 and its target gene ECT2 may be associated with the aggressive tumor progression of human osteosarcoma. Of note, the combined miR-223 down-regulation and Ect2 up-regulation may be a possible marker of poor prognosis in this malignancy.