title: Identification of a blood-borne miRNA signature of synovial sarcoma.
abstract: BACKGROUND
  Synovial 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).
  
  
  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, 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.
  
  
  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. 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.
  
  
  CONCLUSIONS
  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. It even distinguishes synovial sarcoma from other sarcoma subtypes, thus potentially serving as a specific biomarker for synovial sarcoma.
authors.affiliation: Department of Plastic and Hand Surgery, University Medical Center Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany. alba.fricke@uniklinik-freiburg.de.
authors.forename: Alba
authors.initials: A
authors.lastname: Fricke
authors.affiliation: Department of Plastic and Hand Surgery, University Medical Center Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany. prisca.viola.ullrich@uniklinik-freiburg.de.
authors.forename: Prisca V
authors.initials: PV
authors.lastname: Ullrich
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany. juergen.heinz@uniklinik-freiburg.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Heinz
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany. dietmar.pfeifer@uniklinik-freiburg.de.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pfeifer
authors.affiliation: Department of Radiation Oncology, University Medical Center Freiburg, Robert-Koch-Straße 3, 79106, Freiburg, Germany. jutta.scholber@uniklinik-freiburg.de.
authors.forename: Jutta
authors.initials: J
authors.lastname: Scholber
authors.affiliation: Department of Orthopaedics and Traumatology, University Medical Center Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany. georg.herget@uniklinik-freiburg.de.
authors.forename: Georg W
authors.initials: GW
authors.lastname: Herget
authors.affiliation: Department of Orthopaedics and Traumatology, University Medical Center Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany. oliver.hauschild@uniklinik-freiburg.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hauschild
authors.affiliation: Institute for Surgical Pathology, University Medical Center Freiburg, Breisacher Str. 115a, 79106, Freiburg, Germany. peter.bronsert@uniklinik-freiburg.de.|Tumorbank Comprehensive Cancer Center Freiburg, Breisacher Str. 115a, 79106, Freiburg, Germany. peter.bronsert@uniklinik-freiburg.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Bronsert
authors.affiliation: Department of Plastic and Hand Surgery, University Medical Center Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany. bjoern.stark@uniklinik-freiburg.de.
authors.forename: G Björn
authors.initials: GB
authors.lastname: Stark
authors.affiliation: Department of Plastic and Hand Surgery, University Medical Center Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany. holger.bannasch@uniklinik-freiburg.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Bannasch
authors.affiliation: Department of Plastic and Hand Surgery, University Medical Center Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany. steffen.eisenhardt@uniklinik-freiburg.de.
authors.forename: Steffen U
authors.initials: SU
authors.lastname: Eisenhardt
authors.affiliation: Department of Plastic and Hand Surgery, University Medical Center Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany. david.braig@uniklinik-freiburg.de.
authors.forename: David
authors.initials: D
authors.lastname: Braig
mesh_terms: D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D013584:Sarcoma, Synovial / Q000097:blood / Q000235:genetics*; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs