Article
Identification of a blood-borne miRNA signature of synovial sarcoma
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Published: | September 28, 2015 |
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Background: Synovial sarcomas account for approximately 10% of all soft-tissue tumors and occur most frequently in young adults. A specific translocation in this sarcoma induces fusion of the SYT gene on chromosome 18 to the SSX genes on chromosome X, leading to proliferation of the tumor cells. The need for non-invasive biomarkers indicating recurrence and activity of this disease has sparked research into short non-coding RNA known as microRNA (miRNA).
Patients and Methods: Blood samples of patients with active synovial sarcoma and of synovial sarcoma patients in complete remission as well as of healthy donors and patients with active leiomyosarcoma were collected. Whole blood RNA was extracted and samples of patients with active synovial sarcoma and of healthy donors were analyzed using an Affymetrix GeneChip miRNA Array v. 4.0. qRT-PCR was carried out to confirm a panel of miRNAs which where differentially expressed in the miRNA array. This miRNA-panel was further evaluated in patients with synovial sarcoma in complete remission and patients with active leiomyosarcoma.
Results: Unsupervised hierarchical clustering of the miRNA arrays separated patients with active synovial sarcoma from healthy controls. A panel of seven miRNAs (miR-99a-5p, miR-146b-5p, miR-148b-3p, miR-195-5p, miR-223-3p, miR-500b-3p and miR-505-3p) was further validated by qRT-PCR to be significantly upregulated in synovial sarcoma patients. qRT-PCR also showed a significant upregulation of these miRNAs in patients with active synovial sarcoma compared to patients with synovial sarcoma in complete remission. Moreover, five of the analyzed miRNAs (miR-146b-5p, miR-148b-3p, miR-223-3p, miR-500b-3p and miR-505-3p) were shown to be significantly upregulated in synovial sarcoma patients compared to leiomyosarcoma patients.
Conclusion: Our results have identified a specific whole blood miRNA signature that may serve as an independent biomarker for the diagnosis of local recurrence or distant metastasis of synovial sarcoma, even distinguishing synovial sarcoma from other sarcoma subtypes such as leiomyosarcoma, thus potentially serving as a specific biomarker for synovial sarcoma.