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(+)w 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.