title: A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool.
abstract: BACKGROUND
  Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults, and its prognosis remains dismal despite intensive research and therapeutic advances. Diagnostic biomarkers would be clinically meaningful to allow for early detection of the tumor and for those cases in which surgery is contraindicated or biopsy results are inconclusive. Recent findings show that GBM cells release microvesicles that contain a select subset of cellular proteins and RNA. The aim of this hypothesis-generating study was to assess the diagnostic potential of miRNAs found in microvesicles isolated from the serum of GBM patients.
  
  
  METHODS
  To control disease heterogeneity, we used patients with newly diagnosed GBM. In the discovery stage, PCR-based TaqMan Low Density Arrays followed by individual quantitative reverse transcriptase polymerase chain reaction were used to test the differences in the miRNA expression levels of serum microvesicles among 25 GBM patients and healthy controls paired by age and sex. The detected noncoding RNAs were then validated in another 50 GBM patients.
  
  
  RESULTS
  We found that the expression levels of 1 small noncoding RNA (RNU6-1) and 2 microRNAs (miR-320 and miR-574-3p) were significantly associated with a GBM diagnosis. In addition, RNU6-1 was consistently an independent predictor of a GBM diagnosis.
  
  
  CONCLUSIONS
  Altogether our results uncovered a small noncoding RNA signature in microvesicles isolated from GBM patient serum that could be used as a fast and reliable differential diagnostic biomarker.
authors.affiliation: Instituto Biodonostia and Hospital Universitario Donostia, San Sebastian, Spain (L.M., N.S., C.B., I.R., A.M., A.L.-M.); Center for Applied Medical Research (CIMA), Pamplona, Spain (E.G., V.S.); Clínica Universidad de Navarra, Pamplona, Spain (J.G.P-L., M.G-H., P.J., S.T., R.D.-V., J.R., A.G., E.X., M.M.A.); Polymat, University of the Basque Country, San Sebastian, Spain (A.A.); IMMA-CIOCC, Fundación Hospital de Madrid, Madrid, Spain (A.A.); Fundación Jimenez-Díaz, Madrid, Spain (J.G.-F.); Complejo Hospitalario de Navarra, Pamplona, Spain (T.T., I.Z.); Pitié-Salpètriere, Paris, France (S.P., J.Y.D.).
authors.forename: Lorea
authors.initials: L
authors.lastname: Manterola
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Guruceaga
authors.forename: Jaime
authors.initials: J
authors.lastname: Gállego Pérez-Larraya
authors.forename: Marisol
authors.initials: M
authors.lastname: González-Huarriz
authors.forename: Patricia
authors.initials: P
authors.lastname: Jauregui
authors.forename: Sonia
authors.initials: S
authors.lastname: Tejada
authors.forename: Ricardo
authors.initials: R
authors.lastname: Diez-Valle
authors.forename: Victor
authors.initials: V
authors.lastname: Segura
authors.forename: Nicolás
authors.initials: N
authors.lastname: Samprón
authors.forename: Cristina
authors.initials: C
authors.lastname: Barrena
authors.forename: Irune
authors.initials: I
authors.lastname: Ruiz
authors.forename: Amaia
authors.initials: A
authors.lastname: Agirre
authors.forename: Angel
authors.initials: A
authors.lastname: Ayuso
authors.forename: Javier
authors.initials: J
authors.lastname: Rodríguez
authors.forename: Alvaro
authors.initials: A
authors.lastname: González
authors.forename: Enric
authors.initials: E
authors.lastname: Xipell
authors.forename: Ander
authors.initials: A
authors.lastname: Matheu
authors.forename: Adolfo
authors.initials: A
authors.lastname: López de Munain
authors.forename: Teresa
authors.initials: T
authors.lastname: Tuñón
authors.forename: Idoya
authors.initials: I
authors.lastname: Zazpe
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Foncillas
authors.forename: Sophie
authors.initials: S
authors.lastname: Paris
authors.forename: Jean Yves
authors.initials: JY
authors.lastname: Delattre
authors.forename: Marta M
authors.initials: MM
authors.lastname: Alonso
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D055354:Exosomes / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C572916:MIRN320 microRNA, human; C558811:MIRN574 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: GBM; biomarkers; diagnosis; exosomes; sncRNAs