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Identification of microRNA biomarkers for response of advanced soft tissue sarcomas to eribulin: Translational results of the EORTC 62052 trial

  • Author Footnotes
    1 These authors contributed equally.
    Erik A.C. Wiemer
    Correspondence
    Corresponding author: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. Fax: +31 10 704 1053. E-mail address: [email protected] (E.A.C. Wiemer).
    Footnotes
    1 These authors contributed equally.
    Affiliations
    Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands
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  • Author Footnotes
    1 These authors contributed equally.
    Agnieszka Wozniak
    Correspondence
    Corresponding author: Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Herestraat 49, Post 815, B-3000 Leuven, Belgium. Fax: +32 16 346901. E-mail address: [email protected] (A. Wozniak).
    Footnotes
    1 These authors contributed equally.
    Affiliations
    Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven, Belgium
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  • Herman Burger
    Affiliations
    Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands
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  • Marcel Smid
    Affiliations
    Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands
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  • Giuseppe Floris
    Affiliations
    Laboratory of Translational Cell and Tissue Research, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium

    Department of Pathology, University Hospitals Leuven, Leuven, Belgium
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  • Axelle Nzokirantevye
    Affiliations
    European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium
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  • Raf Sciot
    Affiliations
    Laboratory of Translational Cell and Tissue Research, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium

    Department of Pathology, University Hospitals Leuven, Leuven, Belgium
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  • Stefan Sleijfer
    Affiliations
    Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands
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  • Patrick Schöffski
    Affiliations
    Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven, Belgium

    Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium
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  • Author Footnotes
    1 These authors contributed equally.
Published:February 16, 2017DOI:https://doi.org/10.1016/j.ejca.2016.12.018

      Highlights

      • Differentially expressed microRNAs (miRNAs) in STS are found in eribulin responders/non-responders.
      • MicroRNA expression levels in soft tissue sarcoma (STS) may predict response to eribulin.
      • miRNA expression identifies different STS subtypes.

      Abstract

      Background

      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.

      Materials and methods

      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.

      Results

      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.

      Conclusions

      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.

      Keywords

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