title: Identification of microRNA biomarkers for response of advanced soft tissue sarcomas to eribulin: Translational results of the EORTC 62052 trial.
abstract: Recent phase II and III clinical trials demonstrated anti-tumour activity of eribulin, a tubulin-interacting cytotoxic agent, in patients with metastatic soft tissue sarcoma (STS). In this exploratory study, we aimed to identify putative microRNA biomarkers that associate with eribulin sensitivity or resistance in STS.
  
  
  
  Archival tumour tissue from primary tumours or metastatic lesions was collected prior to eribulin treatment, from 65 consenting patients involved in the EORTC trial 62052. This phase II study (ClinicalTrials.gov identifier NCT00413192) included multiple subtypes of STS. Tissue was available from 21 leiomyosarcomas, 14 adipocytic sarcomas, 9 synovial sarcomas and 21 other sarcoma histotypes. Total RNA was isolated from formalin-fixed, paraffin-embedded tumour samples and analysed using Taqman®Low Density Arrays to determine microRNA expression profiles. The expression of a total of 756 microRNAs was assessed. Progression-free survival at week 12 (RECIST 1.0) measured as a binary variable, was the primary end-point of the clinical trial and used as a primary response measure for correlative studies. Seventeen of 53 (32.1%) evaluable patients in the analysed subset had non-progressive disease at week 12 and were defined as responders.
  
  
  
  The expression of 26 individual microRNAs (p < 0.05) differed significantly between non-responders and responders. Additional microRNAs of potential relevance were identified when considering the different histological subgroups.
  
  
  
  The expression level of particular microRNAs in STS tissue samples may predict response to eribulin. Further validation studies as well as a preclinical assessment of the underlying molecular mechanisms are required.
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Erik A C
authors.initials: EAC
authors.lastname: Wiemer
authors.affiliation: Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven, Belgium.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wozniak
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Herman
authors.initials: H
authors.lastname: Burger
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Smid
authors.affiliation: Laboratory of Translational Cell and Tissue Research, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium; Department of Pathology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Floris
authors.affiliation: European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium.
authors.forename: Axelle
authors.initials: A
authors.lastname: Nzokirantevye
authors.affiliation: Laboratory of Translational Cell and Tissue Research, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium; Department of Pathology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sleijfer
authors.affiliation: Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven, Belgium; Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schöffski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D005663:Furans / Q000627:therapeutic use*; D006801:Humans; D007659:Ketones / Q000627:therapeutic use*; D007890:Leiomyosarcoma / Q000188:drug therapy; D008080:Liposarcoma / Q000188:drug therapy; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D018204:Neoplasms, Connective and Soft Tissue / Q000188:drug therapy*; D012509:Sarcoma / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005663:Furans; D007659:Ketones; D035683:MicroRNAs; C490954:eribulin; D000095662:Polyether Polyketides
keywords: Adipocytic sarcoma; EORTC 62052; Eribulin; Leiomyosarcoma; Liposarcoma; MiRNA; MicroRNA; Soft tissue sarcoma