title: Expression of lncRNAs in Low-Grade Gliomas and Glioblastoma Multiforme: An In Silico Analysis.
abstract: BACKGROUND
  Each year, over 16,000 patients die from malignant brain cancer in the US. Long noncoding RNAs (lncRNAs) have recently been shown to play critical roles in regulating neurogenesis and brain tumor progression. To better understand the role of lncRNAs in brain cancer, we performed a global analysis to identify and characterize all annotated and novel lncRNAs in both grade II and III gliomas as well as grade IV glioblastomas (glioblastoma multiforme [GBM]).
  
  
  RESULTS
  We determined the expression of all lncRNAs in over 650 brain cancer and 70 normal brain tissue RNA sequencing datasets from The Cancer Genome Atlas (TCGA) and other publicly available datasets. We identified 611 induced and 677 repressed lncRNAs in glial tumors relative to normal brains. Hundreds of lncRNAs were specifically expressed in each of the three lower grade glioma (LGG) subtypes (IDH1/2 wt, IDH1/2 mut, and IDH1/2 mut 1p19q codeletion) and the four subtypes of GBMs (classical, mesenchymal, neural, and proneural). Overlap between the subtype-specific lncRNAs in GBMs and LGGs demonstrated similarities between mesenchymal GBMs and IDH1/2 wt LGGs, with 2-fold higher overlap than would be expected by random chance. Using a multivariate Cox regression survival model, we identified 584 and 282 lncRNAs that were associated with a poor and good prognosis, respectively, in GBM patients. We developed a survival algorithm for LGGs based on the expression of 64 lncRNAs that was associated with patient prognosis in a test set (hazard ratio [HR] = 2.168, 95% CI = 1.765-2.807, p < 0.001) and validation set (HR = 1.921, 95% CI = 1.333-2.767, p < 0.001) of patients from TCGA. The main limitations of this study are that further work is needed to investigate the clinical relevance of our findings, and that validation in an independent dataset is needed to determine the robustness of our survival algorithm.
  
  
  CONCLUSIONS
  This work identifies a panel of lncRNAs that appear to be prognostic in gliomas and provides a critical resource for future studies examining the role of lncRNAs in brain cancers.
authors.affiliation: Department of Pathology, School of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.|Department of Biochemistry, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Reon
authors.affiliation: Department of Biochemistry, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Jordan
authors.initials: J
authors.lastname: Anaya
authors.affiliation: Division of Neuro-Oncology, Neurology Department, University of Virginia Health System, Old Medical School, Charlottesville, Virginia, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: James
authors.identifier: http://orcid.org/0000-0002-5000-8276
authors.initials: J
authors.lastname: Mandell
authors.affiliation: Division of Neuro-Oncology, Neurology Department, University of Virginia Health System, Old Medical School, Charlottesville, Virginia, United States of America.
authors.forename: Benjamin
authors.identifier: http://orcid.org/0000-0001-7372-6062
authors.initials: B
authors.lastname: Purow
authors.affiliation: Division of Neuro-Oncology, Neurology Department, University of Virginia Health System, Old Medical School, Charlottesville, Virginia, United States of America.
authors.forename: Roger
authors.initials: R
authors.lastname: Abounader
authors.affiliation: Department of Biochemistry, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Anindya
authors.initials: A
authors.lastname: Dutta
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D003198:Computer Simulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D005910:Glioma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D062085:RNA, Long Noncoding