title: A microRNA signature profile in EBV+ diffuse large B-cell lymphoma of the elderly.
abstract: Currently, there is no characteristic microRNA (miRNA) expression pattern in Epstein-Barr virus+ diffuse large B-cell lymphoma of the elderly (EBV+DLBCLe). This study aims to characterize a signature profile and identify miRNAs that can be used as biomarkers and alternative therapeutic targets for EBV+DLBCLe. Seventy-one DLBCL patients aged 50 years and older were included and four EBV+ and four EBV- samples were analyzed in two miRNA array platforms (pilot study). A larger multicenter cohort (29 EBV+DLBCLe and 65 EBV-DLBCL patients) was used to validate the results by real-time polymerase chain reaction. In the pilot study, 9% of DLBCL were EBV+DLBCLe by in situ hybridization. In multicenter study, EBV+DLBCLe group showed a predominance of non-germinal center B-cell origin. Overall survival duration of EBV+DLBCLe was significantly inferior to that of EBV-DLBCL patients. We found 10 deregulated miRNAs in the two groups, but only seven were statistically different. We confirmed overexpression of hsa-miR-126, hsa-miR-146a, hsa-miR-146b, hsa-miR-150, and hsa-miR-222 and underexpression of hsa-miR-151 in EBV+DLBCLe cases compared to EBV-DLBCL cases. Hsa-miR-146b and hsa-miR-222 showed high specificity for identifying EBV+DLBCLe. The present study proposed a miRNA signature for EBV+DLBCLe and our findings suggest that hsa-miR-146b and hsa-miR-222 could be biomarkers and therapeutic targets.
authors.affiliation: Universidade Federal de Sao Paulo, UNIFESP, Sao Paulo, Brazil.
authors.forename: Tathiana Azevedo de
authors.initials: TA
authors.lastname: Andrade
authors.affiliation: Hospital de Cancer de Barretos, Barretos, Brazil.
authors.forename: Adriane Feijo
authors.initials: AF
authors.lastname: Evangelista
authors.affiliation: A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Antonio Hugo Froes
authors.initials: AH
authors.lastname: Campos
authors.affiliation: Universidade Federal de Sao Paulo, UNIFESP, Sao Paulo, Brazil.
authors.forename: Wagner Augusto
authors.initials: WA
authors.lastname: Poles
authors.affiliation: Universidade Federal de Sao Paulo, UNIFESP, Sao Paulo, Brazil.
authors.forename: Natalia Morais
authors.initials: NM
authors.lastname: Borges
authors.affiliation: A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Claudia Malheiros Coutinho
authors.initials: CM
authors.lastname: Camillo
authors.affiliation: A.C. Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.affiliation: A.C. Camargo Cancer Center, Sao Paulo, Brazil. Universidade de Campinas, Campinas, Brazil.
authors.forename: Jose
authors.initials: J
authors.lastname: Vassallo
authors.affiliation: Santa Casa de Misericordia de Sao Paulo, Sao Paulo, Brazil.
authors.forename: Roberto Pinto
authors.initials: RP
authors.lastname: Paes
authors.affiliation: Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.
authors.forename: Maria Claudia
authors.initials: MC
authors.lastname: Zerbini
authors.affiliation: Hospital de Cancer de Barretos, Barretos, Brazil.
authors.forename: Cristovam
authors.initials: C
authors.lastname: Scapulatempo
authors.affiliation: Universidade Federal de Sao Paulo, UNIFESP, Sao Paulo, Brazil.
authors.forename: Antonio Correa
authors.initials: AC
authors.lastname: Alves
authors.affiliation: Department of Hematopathology, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
authors.affiliation: Universidade Federal de Sao Paulo, UNIFESP, Sao Paulo, Brazil.
authors.forename: Gisele Wally Braga
authors.initials: GW
authors.lastname: Colleoni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics*; D020031:Epstein-Barr Virus Infections; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000401:mortality / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010865:Pilot Projects; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C542542:MIRN146 microRNA, human; C525710:MIR222, human