1. Department of Orthopaedic Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, PR China
2. Institute of Bone Tumor Affiliated to Tongji University School of Medicine, Shanghai 200072, PR China
*These authors contributed equally to this study and share first authorship. They are all considered Co-first authors.
Circular RNA (circRNA) is associated with human cancers, however, few studies have reported its value in the diagnosis and prognosis prediction of osteosarcoma (OS). In this study, we investigated the expression level of eight selected cancer-related circRNAs including circ-Cdr1as, circ_HIPK3 and circ-ITCH in OS cell lines, tissues and plasmas by quantitative real-time polymerase chain reaction (qRT-PCR) and found that only circ_HIPK3 could stably down-regulate in the OS cell lines, tissues and plasmas than the corresponding controlled. One-way analysis of variance was further conducted to analyze the relationship between circ_HIPK3 expression level and clinic pathological factors of OS patients. Receiver operating characteristic (ROC) curve was built to evaluate the diagnostic values of circ_HIPK3. Circ_HIPK3 expression was significantly correlated with Enneking stage (P=0.042) and lung metastasis (P=0.036). The area under the ROC curve was 0.783 and the sensitivity and specificity were 0.56 and 0.84, respectively. Kaplan-Maier analysis also showed that lower expression of circ_HIPK3 correlated with shorter overall survival time and poor prognosis of OS patients. Besides, function analysis demonstrated that circHIPK3 overexpression significantly suppressed OS cell proliferation, migration and invasion in vitro. Overall, our data suggest that circ_HIPK3 may become a novel potential biomarker for diagnosis and treatment target of OS.
Keywords: circRNA, circ_HIPK3, osteosarcoma, biomarker, progression