title: MicroRNA signature obtained from the comparison of aggressive with indolent non-Hodgkin lymphomas: potential prognostic value in mantle-cell lymphoma.
abstract: OBJECTIVE
  Mantle-cell lymphoma (MCL) has a variable natural history but is incurable with current therapies. MicroRNAs (miRs) are useful in prognostic assessment of cancer. We determined an miR signature defining aggressiveness in B-cell non-Hodgkin lymphomas (NHL) and assessed whether this signature aids in MCL prognosis.
  
  
  METHODS
  We assessed miR expression in a training set of 43 NHL cases. The miR signature was validated in 44 additional cases and examined on a training set of 119 MCL cases from four institutions in Canada. miRs significantly associated with overall survival were examined in an independent cohort of 114 MCL cases to determine association with patient outcome. miR expression was combined with current clinical prognostic factors to develop an enhanced prognostic model in patients with MCL.
  
  
  RESULTS
  Fourteen miRs were differentially expressed between aggressive and indolent NHL; 11 of 14 were validated in an independent set of NHL (excluding MCL). miR-127-3p and miR-615-3p were significantly associated with overall survival in the MCL training set. Their expression was validated in an independent MCL patient set. In comparison with Ki-67, expression of these miRs was more significantly associated with overall survival among patients with MCL. miR-127-3p was combined with Ki-67 to create a new prognostic model for MCL. A similar model was created with miR-615-3p and Mantle Cell Lymphoma International Prognostic Index scores.
  
  
  CONCLUSIONS
  Eleven miRs are differentially expressed between aggressive and indolent NHL. Two novel miRs were associated with overall survival in MCL and were combined with clinical prognostic models to generate novel prognostic data for patients with MCL.
authors.affiliation: Ontario Cancer Institute, University Health Network.
authors.forename: Rashmi S
authors.initials: RS
authors.lastname: Goswami
authors.forename: Eshetu G
authors.initials: EG
authors.lastname: Atenafu
authors.forename: Yali
authors.initials: Y
authors.lastname: Xuan
authors.forename: Levi
authors.initials: L
authors.lastname: Waldron
authors.forename: Patricia P
authors.initials: PP
authors.lastname: Reis
authors.forename: Thomas
authors.initials: T
authors.lastname: Sun
authors.forename: Alessandro
authors.initials: A
authors.lastname: Datti
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: John
authors.initials: J
authors.lastname: Kuruvilla
authors.forename: David J
authors.initials: DJ
authors.lastname: Good
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
authors.forename: Alanna J
authors.initials: AJ
authors.lastname: Church
authors.forename: Wilson S
authors.initials: WS
authors.lastname: Lam
authors.forename: Tara
authors.initials: T
authors.lastname: Baetz
authors.forename: David P
authors.initials: DP
authors.lastname: Lebrun
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Sehn
authors.forename: Pedro
authors.initials: P
authors.lastname: Farinha
authors.forename: Igor
authors.initials: I
authors.lastname: Jurisica
authors.forename: Denis J
authors.initials: DJ
authors.lastname: Bailey
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Michael
authors.initials: M
authors.lastname: Crump
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D016612:Paraffin Embedding; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs