title: miRNA expression in diffuse large B-cell lymphoma treated with chemoimmunotherapy.
abstract: Diffuse large B-cell lymphoma (DLBCL) prognostication requires additional biologic markers. miRNAs may constitute markers for cancer diagnosis, outcome, or therapy response. In the present study, we analyzed the miRNA expression profile in a retrospective multicenter series of 258 DLBCL patients uniformly treated with chemoimmunotherapy. Findings were correlated with overall survival (OS) and progression-free survival (PFS). miRNA and gene-expression profiles were studied using microarrays in an initial set of 36 cases. A selection of miRNAs associated with either DLBCL molecular subtypes (GCB/ABC) or clinical outcome were studied by multiplex RT-PCR in a test group of 240 cases with available formalin-fixed, paraffin-embedded (FFPE) diagnostic samples. The samples were divided into a training set (123 patients) and used to derive miRNA-based and combined (with IPI score) Cox regression models in an independent validation series (117 patients). Our model based on miRNA expression predicts OS and PFS and improves upon the predictions based on clinical variables. Combined models with IPI score identified a high-risk group of patients with a 2-year OS and a PFS probability of < 50%. In summary, a precise miRNA signature is associated with poor clinical outcome in chemoimmunotherapy-treated DLBCL patients. This information improves upon IPI-based predictions and identifies a subgroup of candidate patients for alternative therapeutic regimens.
authors.affiliation: Lymphoma Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Montes-Moreno
authors.forename: Nerea
authors.initials: N
authors.lastname: Martinez
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sanchez-Espiridión
authors.forename: Ramon
authors.initials: R
authors.lastname: Díaz Uriarte
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Rodriguez
authors.forename: Anabel
authors.initials: A
authors.lastname: Saez
authors.forename: Carlos
authors.initials: C
authors.lastname: Montalbán
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Gomez
authors.forename: David G
authors.initials: DG
authors.lastname: Pisano
authors.forename: Juan Fernando
authors.initials: JF
authors.lastname: García
authors.forename: Eulogio
authors.initials: E
authors.lastname: Conde
authors.forename: Eva
authors.initials: E
authors.lastname: Gonzalez-Barca
authors.forename: Andres
authors.initials: A
authors.lastname: Lopez
authors.forename: Manuela
authors.initials: M
authors.lastname: Mollejo
authors.forename: Carlos
authors.initials: C
authors.lastname: Grande
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Martinez
authors.forename: Cherie
authors.initials: C
authors.lastname: Dunphy
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.forename: Gabrielle B
authors.initials: GB
authors.lastname: Rocque
authors.forename: Julie
authors.initials: J
authors.lastname: Chang
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Go
authors.forename: Carlo
authors.initials: C
authors.lastname: Visco
authors.forename: Zijun
authors.initials: Z
authors.lastname: Xu-Monette
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Piris
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D046228:Microarray Analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D035683:MicroRNAs