Identification of a blood-borne miRNA signature of synovial sarcoma

Abstract

BackgroundSynovial sarcoma 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).MethodsBlood 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, MPNST, Ewing sarcoma and liposarcoma 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, MPNST, Ewing sarcoma and liposarcoma as well as in an independent cohort of synovial sarcoma patients.ResultsUnsupervised 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. Moreover, most of the analyzed miRNAs were shown to be significantly upregulated in synovial sarcoma patients compared to leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma patients. Validation of the miRNA panel in an independent cohort of synovial sarcoma patients confirmed higher expression levels compared to healthy controls and patients in complete remission.ConclusionOur 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. It even distinguishes synovial sarcoma from other sarcoma subtypes, thus potentially serving as a specific biomarker for synovial sarcoma.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0424-z) contains supplementary material, which is available to authorized users.

Exosome-Derived miR-25-3p and miR-92a-3p Stimulate Liposarcoma Progression

“…However, to the best of our knowledge, a study reporting an array analysis characterizing circulating miRNAs in LPS has not yet been described. Previously Fricke et al identified a blood-borne miRNAs signature in synovial sarcoma (24). Recently Boro et al suggested that miR-155 might be a diagnostic marker for DDLPS, but in his work only five DDLPS patients were analyzed (25).…”

Mir505–3p regulates axonal development via inhibiting the autophagy pathway by targeting Atg12

“…Previously, Mir505-3p has been identified as an indicator of tumor genesis and development. It is supposed to be one among potential early diagnostic markers for cervical carcinogenesis, 54 a biomarker for local recurrence or distant metastasis of synovial sarcoma, 55 and a prognostic biomarker for breast cancer. 56 Besides, Mir505/Mir505-3p is proven to be a tumor repressor.…”

MicroRNA Expression Patterns of CD8+ T Cells in Acute and Chronic Brucellosis

“…Indeed, some miRNAs that have been previously linked to carcinogenesis of different organs and tissues, such as miR-2861 [47, 48], miR-4530 [49], miR-638 [50], miR-371b-5p [51], miR-1225-5p [52, 53], miR-296-5p [54, 55], miR-4787-5p [56], miR-4281 [57], miR-4455 [58], miR-197-3p [59], miR-369-5p [60, 61] and miR-505-3p [62] which were found to be altered in brucellosis in our analysis.…”