title: Altered MicroRNA Expression Is Associated with Tumor Grade, Molecular Background and Outcome in Childhood Infratentorial Ependymoma.
abstract: BACKGROUND
  Ependymal tumors are the third most common group of brain tumors in children, accounting for about 10% of all primary brain neoplasms. According to the current WHO classification, they comprise four entities with the most frequent ependymoma and anaplastic ependymoma. The most of pediatric tumors are located within the posterior fossa, with a tendency to infiltrate the vital brain structures. This limits surgical resection and poses a considerable clinical problem. Moreover, there are no appropriate outcome prognostic factors besides the extent of surgical resection. Despite definition of molecular subgroups, the majority of childhood ependymomas present a balanced genome, which makes it difficult to establish molecular prognostic factors.
  
  
  METHODS
  The purpose of our study was to explore whether miRNA expression could be used as prognostic markers in pediatric infratentorial ependymomas. We also performed a mRNA expression pattern analysis of NELL2 and LAMA2 genes, with immunohistochemical illustrations of representative cases. The miRNA and mRNA expression was measured in 53 pediatric infratentorial ependymomas using a real-time quantitative PCR.
  
  
  RESULTS
  Three miRNAs were shown to efficiently differentiate between grade II and III ependymomas: miR-17-5p, miR-19a-3p, and miR-106b-5p. Survival analysis showed that the probabilities of overall (p = 0.036) and event-free survival (p = 0.002) were reduced with higher than median miRNA expression levels of miR-17-5p. Using multivariate analysis adjusted for patient's age, sex, tumor grade and localization, we showed statistically significant associations with event-free survival (p = 0004) and borderline statistical significance with overall survival (p = 0.057) for miR-17-5p. Correlation analysis of miR-19a, miR-17-5p, miR-106b revealed that their expression levels were significantly correlated with EZH2 expression, suggested marker of PFA ependymomas. Furthermore, lower expression level of LAMA2 mRNA was shown to be associated with an increased risk of death in covariate-adjusted analyses.
  
  
  CONCLUSIONS
  Our data provide a better understanding of pediatric ependymoma and suggests the presence of plausible molecular biomarkers connected with the outcome.
authors.affiliation: Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zakrzewska
authors.affiliation: Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Fendler
authors.affiliation: Department of Neurosurgery, Polish Mother Memorial Hospital Research Institute, Lodz, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Zakrzewski
authors.affiliation: Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Sikorska
authors.affiliation: Department of Pathology, Children's Memorial Health Institute, Warsaw, Poland.|Department of Experimental and Clinical Neuropathology, M. Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Wiesława
authors.initials: W
authors.lastname: Grajkowska
authors.affiliation: Department of Pediatric Oncology, Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Bożenna
authors.initials: B
authors.lastname: Dembowska-Bagińska
authors.affiliation: Department of Pediatric Oncology, Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Filipek
authors.affiliation: Third Municipal Hospital in Lodz, Lodz, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Stefańczyk
authors.affiliation: Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland.
authors.forename: Paweł P
authors.initials: PP
authors.lastname: Liberski
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000209:etiology / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D018076:DNA, Complementary / Q000235:genetics; D018572:Disease-Free Survival; D004806:Ependymoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D015192:Infratentorial Neoplasms / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D018076:DNA, Complementary; C542541:MIRN106 microRNA, human; C524941:MIRN17 microRNA, human; C549214:MIRN19A microRNA, human; D035683:MicroRNAs