In this study, the results showed that the serum level of miR-217 was significantly decreased in osteosarcoma patients comparing with healthy participates. Moreover, serum miR-217 level can be used as a superior marker to discriminate osteosarcoma patients from healthy subjects. Furthermore, we evaluated the significance of serum miR-217 in predicting prognosis of osteosarcoma patients and found that a low serum miR-217 level was significantly associated with shorter survival in osteosarcoma patients. We also observed a significant association between serum miR-217 level and classical unfavorable clinical characteristics for osteosarcoma patients. Based on such results, we suggested that miR-217 can be used as a diagnostic biomarker for osteosarcoma patients, which also can serve as a promising prognostic indictor.
MiR-217, as a novel tumor biomarker, play critical roles in biological process of cancer development(25). The miR-217 has been confirmed as a potential tumor suppressor in many malignancies including osteosarcoma(26, 27). Shen et al. reported that miR-217 was decreased both in cancer cell lines and tissues, which was significantly correlated with distant metastasis, and functioned as a tumor suppressive miRNA and inhibits the osteosarcoma tumorigenesis through targeting WASF3(28). Moreover, miR-217 may be involved in inhibiting of tumor cells proliferation and metastasis through targeting KRAS oncogene(29). In our study, miR-217 was remarkably downregulated in osteosarcoma patients and significantly correlated with poor prognosis, which are consistent with the previous studies mentioned above.
However, the underlying function and origin of serum miR-217 in malignancy have not yet been fully understood. Several potential mechanisms for circulating miRNAs releasing have been reported, including passive leakage from cells in setting of chronic inflammation or injury, active secretion, complex formation with lipoproteins or RNA binding proteins(30–32). Yan et al. reported that serum miR-217 expression was significantly decreased in acute myeloid leukemia (AML) patients compared to controls, which was identified as an independent marker for the diagnosis and prognosis of AML(33). It has been reported that low expressions of certain miRNAs were remarkably associated with advanced cancer stage(34). In this study, we found that low serum level of miR-217 was significantly associated with clinical stage of osteosarcoma patients, which is consistence with previous studies.
Our study firstly reported that the downregulation of serum miR-217 level in a considerable scale osteosarcoma patients’ group, which can serve as a serum diagnostic and prognostic biomarker, as well as a novel therapeutic target for osteosarcoma. However, there were several limitations in this study. One limitation was a single center, small sample size and retrospective design of study. A large-scale, prospective and multicenter study is required to furtherly reevaluate such results. Furthermore, the underlying roles and mechanisms of miR-217 in development of osteosarcoma have not yet been fully evaluated. Future experiments are needed to be performed to elucidate the mechanisms of serum miR-217 in carcinogenesis.