Prognostic microRNAs in high-grade glioma reveal a link to oligodendrocyte precursor differentiation
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https://doi.org/10.18632/oncoscience.112
Josie Hayes1, Helene Thygesen1 Alastair Droop1, Thomas A. Hughes2, David Westhead3, Sean E. Lawler4, Heiko Wurdak1 and Susan Short1
1 Leeds Institute of Cancer and Pathology, University of Leeds, St James’s University Hospital, Leeds, UK
2 Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, St James’s University Hospital, Leeds, UK
3 Institute of Molecular and Cellular Biology, Faculty of Biological Sciences and Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK
4 Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Correspondence:
Heiko Wurdak, email:
Correspondence:
Susan Short, email:
Keywords: glioma, oligodendrocyte, glioblastoma, astrocytoma, microRNA, prognosis
Received: November 4, 2014 Accepted: December 22, 2014 Published: December 26, 2014
Abstract
MicroRNA expression can be exploited to define tumor prognosis and stratification for precision medicine. It remains unclear whether prognostic microRNA signatures are exclusively tumor grade and/or molecular subtype-specific, or whether common signatures of aggressive clinical behavior can be identified. Here, we defined microRNAs that are associated with good and poor prognosis in grade III and IV gliomas using data from The Cancer Genome Atlas. Pathway analysis of microRNA targets that are differentially expressed in good and poor prognosis glioma identified a link to oligodendrocyte development. Notably, a microRNA expression profile that is characteristic of a specific oligodendrocyte precursor cell type (OP1) correlates with microRNA expression from 597 of these tumors and is consistently associated with poor patient outcome in grade III and IV gliomas. Our study reveals grade-independent and subtype-independent prognostic molecular signatures in high-grade glioma and provides a framework for investigating the mechanisms of brain tumor aggressiveness.
