TY - JOUR
T1 - A microRNA signature profile in EBV+ diffuse large B-cell lymphoma of the elderly
AU - de Andrade, Tathiana Azevedo
AU - Evangelista, Adriane Feijo
AU - Froes Campos, Antonio Hugo
AU - Poles, Wagner Augusto
AU - Borges, Natalia Morais
AU - Coutinho Camillo, Claudia Malheiros
AU - Soares, Fernando Augusto
AU - Vassallo, Jose
AU - Paes, Roberto Pinto
AU - Zerbini, Maria Claudia
AU - Scapulatempo, Cristovam
AU - Alves, Antonio Correa
AU - Young, Ken H.
AU - Colleoni, Gisele Wally Braga
PY - 2014
Y1 - 2014
N2 - 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. Seventyone 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, hsamiR- 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.
AB - 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. Seventyone 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, hsamiR- 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.
KW - DLBCL
KW - EBV
KW - Elderly
KW - MicroRNA
UR - http://www.scopus.com/inward/record.url?scp=84920020064&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84920020064&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.2952
DO - 10.18632/oncotarget.2952
M3 - Article
C2 - 25544772
AN - SCOPUS:84920020064
SN - 1949-2553
VL - 5
SP - 11813
EP - 11826
JO - Oncotarget
JF - Oncotarget
IS - 23
ER -