A microRNA signature profile in EBV+ diffuse large B-cell lymphoma of the elderly

Abstract

// Tathiana Azevedo de Andrade 1 , Adriane Feijo Evangelista 2 , Antonio Hugo Froes Campos 3 , Wagner Augusto Poles 1 , Natalia Morais Borges 1 , Claudia Malheiros Coutinho Camillo 3 , Fernando Augusto Soares 3 , Jose Vassallo 3,4 , Roberto Pinto Paes 5 , Maria Claudia Zerbini 6 , Cristovam Scapulatempo 2 , Antonio Correa Alves 1 , Ken H. Young 7,* and Gisele Wally Braga Colleoni 1,* 1 Universidade Federal de Sao Paulo, UNIFESP, Sao Paulo, Brazil 2 Hospital de Cancer de Barretos, Barretos, Brazil 3 A.C. Camargo Cancer Center, Sao Paulo, Brazil 4 Universidade de Campinas, Campinas, Brazil 5 Santa Casa de Misericordia de Sao Paulo, Sao Paulo, Brazil 6 Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil 7 Department of Hematopathology, MD Anderson Cancer Center, Houston, Texas, USA * Both are senior authors Correspondence: Tathiana Andrade, email: // Gisele Colleoni, email: // Keywords : DLBCL, EBV, elderly, microRNA Received : October 03, 2014 Accepted : December 09, 2014 Published : December 10, 2014 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.