title: MicroRNAs are independent predictors of outcome in diffuse large B-cell lymphoma patients treated with R-CHOP.
abstract: OBJECTIVE
  Diffuse large B-cell lymphoma (DLBCL) heterogeneity has prompted investigations for new biomarkers that can accurately predict survival. A previously reported 6-gene model combined with the International Prognostic Index (IPI) could predict patients' outcome. However, even these predictors are not capable of unambiguously identifying outcome, suggesting that additional biomarkers might improve their predictive power.
  
  
  METHODS
  We studied expression of 11 microRNAs (miRNA) that had previously been reported to have variable expression in DLBCL tumors. We measured the expression of each miRNA by quantitative real-time PCR analyses in 176 samples from uniformly treated DLBCL patients and correlated the results to survival.
  
  
  RESULTS
  In a univariate analysis, the expression of miR-18a correlated with overall survival (OS), whereas the expression of miR-181a and miR-222 correlated with progression-free survival (PFS). A multivariate Cox regression analysis including the IPI, the 6-gene model-derived mortality predictor score and expression of the miR-18a, miR-181a, and miR-222, revealed that all variables were independent predictors of survival except the expression of miR-222 for OS and the expression of miR-18a for PFS.
  
  
  CONCLUSIONS
  The expression of specific miRNAs may be useful for DLBCL survival prediction and their role in the pathogenesis of this disease should be examined further.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology and Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA.
authors.forename: Alvaro J
authors.initials: AJ
authors.lastname: Alencar
authors.forename: Raquel
authors.initials: R
authors.lastname: Malumbres
authors.forename: Goldi A
authors.initials: GA
authors.lastname: Kozloski
authors.forename: Ranjana
authors.initials: R
authors.lastname: Advani
authors.forename: Neha
authors.initials: N
authors.lastname: Talreja
authors.forename: Shideh
authors.initials: S
authors.lastname: Chinichian
authors.forename: Javier
authors.initials: J
authors.lastname: Briones
authors.forename: Yasodha
authors.initials: Y
authors.lastname: Natkunam
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Sehn
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Rob
authors.initials: R
authors.lastname: Tibshirani
authors.forename: Izidore S
authors.initials: IS
authors.lastname: Lossos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016000:Cluster Analysis; D003520:Cyclophosphamide / Q000627:therapeutic use; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D004317:Doxorubicin / Q000627:therapeutic use; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D014750:Vincristine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D035683:MicroRNAs; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D011241:Prednisone