Osteosarcoma is the most common human primary malignant bone tumor in children 
and young adults. Sensitive and non-invasive biomarkers that can facilitate 
disease detection at early stage are highly desirable to improve survival rate 
and help to determine optimized treatment for osteosarcoma. The small non-coding 
RNAs, microRNAs (miRNAs), have recently been identified as critical regulators 
for various diseases including cancer and may represent a novel class of cancer 
biomarkers. In this study, we aimed to detect the potential of circulating 
miRNAs as biomarkers for osteosarcoma. Levels of six candidate miRNAs (miR-21, 
miR-199a-3p, miR-143, miR-34, miR-140, and miR-132) that were previously 
demonstrated to be regulated in osteosarcoma were examined in plasma of 40 
osteosarcoma patients and 40 matched healthy controls by quantitative 
reverse-transcription polymerase chain reaction assays. The results showed that 
circulating levels of miR-21 were significantly higher in osteosarcoma patients 
than controls, while miR-199a-3p and miR-143 were decreased in osteosarcoma 
patients. We replicated the findings in an independent study of 40 osteosarcoma 
patients and 40 matched controls and confirmed the results. Receiver operating 
characteristics curve analysis of the combined populations demonstrated that the 
three-miRNA signature could discriminate cases from controls with an area under 
the curve of 0.953 (95 % CI 0.924-0.984). In addition, circulating miR-21 and 
miR-143 were correlated with both metastasis status and histological subtype of 
the patients, while miR-199a-3p only correlated with histological subtype. Our 
data suggest that altered levels of circulating miRNAs might have great 
potential to serve as novel, non-invasive biomarkers for osteosarcoma.