Journal
ONCOTARGET
Volume 8, Issue 20, Pages 33375-33392Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.16498
Keywords
microRNA; liquid biopsy; osteosarcoma; biomarker; prognosis
Categories
Funding
- Japan Orthopaedics and Traumatology Research Foundation, Inc. [311]
- NOVARTIS Foundation for the Promotion of Science, JSPS KAKENHI Grant [16K20054]
- JSPS KAKENHI Grant [16H05449]
- Grants-in-Aid for Scientific Research [16H05449, 16H02676, 16K20054] Funding Source: KAKEN
Ask authors/readers for more resources
Background: Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. Methods: Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort. Results: Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17-5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase. Conclusions: Serum-based circulating miR-25-3p may serve as a non-invasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available