Combined elevation of microRNA-196a and microRNA-196b in sera predicts unfavorable prognosis in patients with osteosarcomas

血清中microRNA-196a和microRNA-196b联合升高预示骨肉瘤患者预后不良

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Abstract

AIM: To investigate whether the aberrant expression of microRNA (miR)-196a and miR-196b can be used as potential prognostic markers of human osteosarcoma. METHODS: Quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis was performed to detect the expression levels of miR-196a and miR-196b in osteosarcoma tissues and patients' sera. RESULTS: Expression levels of miR-196a and miR-196b in osteosarcoma tissues were both significantly higher than those in noncancerous bone tissues (both p<0.001), in line with which, the serum levels of the two miRNAs were also markedly upregulated in patients with osteosarcomas compared with healthy controls (both p<0.001). Then, the elevation of serum miR-196a and miR-196b levels both more frequently occurred in osteosarcoma patients with high tumor grade (p=0.008 and 0.01, respectively), positive metastasis (p=0.001 and 0.006, respectively) and recurrence (p=0.001 and 0.006, respectively). Moreover, high serum miR-196a, high serum miR-196b and conjoined expression of miR-196a/miR-196b were all independent prognostic factors for OS (overall survival) and DFS (disease-free survival) of osteosarcoma patients. CONCLUSION: Our present data indicate the involvement of miR-196a and miR-196b upregulation in the pathogenesis of osteosarcoma. More importantly, the altered levels of circulating miR-196a and miR-196b might have great potential to serve as novel and non-invasive prognostic factors for this malignancy.

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