title: Prognostic microRNAs in high-grade glioma reveal a link to oligodendrocyte precursor differentiation.
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.
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, St James's University Hospital, Leeds, UK.
authors.forename: Josie
authors.initials: J
authors.lastname: Hayes
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, St James's University Hospital, Leeds, UK.
authors.forename: Helene
authors.initials: H
authors.lastname: Thygesen
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, St James's University Hospital, Leeds, UK.
authors.forename: Alastair
authors.initials: A
authors.lastname: Droop
authors.affiliation: Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, St James's University Hospital, Leeds, UK.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Hughes
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Westhead
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Sean E
authors.initials: SE
authors.lastname: Lawler
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, St James's University Hospital, Leeds, UK.
authors.forename: Heiko
authors.initials: H
authors.lastname: Wurdak
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, St James's University Hospital, Leeds, UK.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Short
keywords: astrocytoma; glioblastoma; glioma; microRNA; oligodendrocyte; prognosis