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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Article info
Publication history
Published online: February 16, 2017
Accepted:
December 24,
2016
Received in revised form:
December 8,
2016
Received:
October 16,
2016
Identification
Copyright
© 2017 Elsevier Ltd. All rights reserved.
