Construction and analysis of a ceRNA-ceRNA network reveals two potential prognostic modules regulated by hsa-miR-335-5p in osteosarcoma

Osteosarcoma is an aggressive cancer of the skeletal system, which is associated with a poor prognosis due to the high recurrence rate. Although previous studies have revealed that competitive endogenous RNAs (ceRNAs) are involved in various biological processes in the physiology and development of osteosarcoma, the roles of ceRNAs in osteosarcoma recurrence remain largely unexplored. The present study constructed a ceRNA-ceRNA network for osteosarcoma by systematically integrating matched expression profiles for microRNAs (miRNAs/miRs) and mRNAs, and identified two ceRNA-mediated modules that were associated with recurrence in patients with osteosarcoma. A multivariate Cox regression analysis demonstrated that the recurrence-free prognosis associated with the expression of the two modules was independent of other clinical factors. In addition, hsa-miR-335-3p was identified as an upstream regulating factor for both modules. In conclusion, the results of the present study suggested that ceRNAs may act as potential therapeutic biomarkers for predicting the recurrence of osteosarcoma, and may help to identify patients with osteosarcoma at a high risk of recurrence, who may benefit from adjuvant therapy.