title: Microrna expression signatures predict patient progression and disease outcome in pediatric embryonal central nervous system neoplasms.
abstract: BACKGROUND
  Although, substantial experimental evidence related to diagnosis and treatment of pediatric central nervous system (CNS) neoplasms have been demonstrated, the understanding of the etiology and pathogenesis of the disease remains scarce. Recent microRNA (miRNA)-based research reveals the involvement of miRNAs in various aspects of CNS development and proposes that they might compose key molecules underlying oncogenesis. The current study evaluated miRNA differential expression detected between pediatric embryonal brain tumors and normal controls to characterize candidate biomarkers related to diagnosis, prognosis and therapy.
  
  
  METHODS
  Overall, 19 embryonal brain tumors; 15 Medulloblastomas (MBs) and 4 Atypical Teratoid/Rabdoid Tumors (AT/RTs) were studied. As controls, 13 samples were used; The First-Choice Human Brain Reference RNA and 12 samples from deceased children who underwent autopsy and were not present with any brain malignancy. RNA extraction was carried out using the Trizol method, whilst miRNA extraction was performed with the mirVANA miRNA isolation kit. The experimental approach included miRNA microarrays covering 1211 miRNAs. Quantitative Real-Time Polymerase Chain Reaction was performed to validate the expression profiles of miR-34a and miR-601 in all 32 samples initially screened with miRNA microarrays and in an additional independent cohort of 30 patients (21MBs and 9 AT/RTs). Moreover, meta-analyses was performed in total 27 embryonal tumor samples; 19 MBs, 8 ATRTs and 121 control samples. Twelve germinomas were also used as an independent validation cohort. All deregulated miRNAs were correlated to patients' clinical characteristics and pathological measures.
  
  
  RESULTS
  In several cases, there was a positive correlation between individual miRNA expression levels and laboratory or clinical characteristics. Based on that, miR-601 could serve as a putative tumor suppressor gene, whilst miR-34a as an oncogene. In general, miR-34a demonstrated oncogenic roles in all pediatric embryonal CNS neoplasms studied.
  
  
  CONCLUSIONS
  Deeper understanding of the aberrant miRNA expression in pediatric embryonal brain tumors might aid in the development of tumor-specific miRNA signatures, which could potentially afford promising biomarkers related to diagnosis, prognosis and patient targeted therapy.
authors.forename: Maria
authors.initials: M
authors.lastname: Braoudaki
authors.forename: George I
authors.initials: GI
authors.lastname: Lambrou
authors.forename: Krinio
authors.initials: K
authors.lastname: Giannikou
authors.forename: Vasilis
authors.initials: V
authors.lastname: Milionis
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Stefanaki
authors.forename: Diane K
authors.initials: DK
authors.lastname: Birks
authors.forename: Neophytos
authors.initials: N
authors.lastname: Prodromou
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Kolialexi
authors.forename: Antonis
authors.initials: A
authors.lastname: Kattamis
authors.forename: Chara A
authors.initials: CA
authors.lastname: Spiliopoulou
authors.forename: Fotini
authors.initials: F
authors.lastname: Tzortzatou-Stathopoulou
authors.forename: Emmanouel
authors.initials: E
authors.lastname: Kanavakis
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000378:metabolism; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D013724:Teratoma / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D035683:MicroRNAs