title: Expression of miR-487b and miR-410 encoded by 14q32.31 locus is a prognostic marker in neuroblastoma.
abstract: BACKGROUND
  Combination of age at diagnosis, stage and MYCN amplification stratifies neuroblastoma into low-risk and high-risk. We aimed to establish whether a microRNA (miRNA) signature could be associated with prognosis in both groups.
  
  
  METHODS
  Microarray expression profiling of human miRNAs and quantitative reverse-transcriptase PCR of selected miRNAs were performed on a preliminary cohort of 13 patients. Results were validated on an independent cohort of 214 patients. The relationship between miRNA expression and the overall or disease-free survival was analysed on the total cohort of 227 patients using the log-rank test and the multivariable Cox proportional hazard model.
  
  
  RESULTS
  A total of 15 of 17 miRNAs that discriminated high-risk from low-risk neuroblastoma belonged to the imprinted human 14q32.31 miRNA cluster and two, miR-487b and miR-410, were significantly downregulated in the high-risk group. Multivariable analyses showed miR-487b expression as associated with overall survival and disease-free survival in the whole cohort, independently of clinical covariates. Moreover, miR-487b and miR-410 expression was significantly associated with disease-free survival of the non-MYCN-amplified favourable neuroblastoma: localised (stage 1, 2 and 3) and stage 4 of infant <18 months.
  
  
  CONCLUSIONS
  Expression of miR-487b and miR-410 shows predictive value beyond the classical high-/low-risk stratification and is a biomarker of relapse in favourable neuroblastoma.
authors.affiliation: CNRS UMR 8126, University Paris-Sud 11, Institut Gustave Roussy, 114 rue Edouard, Villejuif F-94805, France.
authors.forename: C-H
authors.initials: CH
authors.lastname: Gattolliat
authors.forename: L
authors.initials: L
authors.lastname: Thomas
authors.forename: S A
authors.initials: SA
authors.lastname: Ciafrè
authors.forename: G
authors.initials: G
authors.lastname: Meurice
authors.forename: G
authors.initials: G
authors.lastname: Le Teuff
authors.forename: B
authors.initials: B
authors.lastname: Job
authors.forename: C
authors.initials: C
authors.lastname: Richon
authors.forename: V
authors.initials: V
authors.lastname: Combaret
authors.forename: P
authors.initials: P
authors.lastname: Dessen
authors.forename: D
authors.initials: D
authors.lastname: Valteau-Couanet
authors.forename: E
authors.initials: E
authors.lastname: May
authors.forename: P
authors.initials: P
authors.lastname: Busson
authors.forename: S
authors.initials: S
authors.lastname: Douc-Rasy
authors.forename: J
authors.initials: J
authors.lastname: Bénard
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D002883:Chromosomes, Human, Pair 14; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C568527:MIRN410 microRNA, human; C568526:MIRN487 microRNA, human; D035683:MicroRNAs