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

Oncotarget. 2014 Dec 15;5(23):11813-26. doi: 10.18632/oncotarget.2952.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Biomarkers, Tumor / genetics*
  • Epstein-Barr Virus Infections
  • Female
  • Humans
  • In Situ Hybridization
  • Kaplan-Meier Estimate
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / virology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Pilot Projects
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Tissue Array Analysis
  • Transcriptome*

Substances

  • Biomarkers, Tumor
  • MIRN146 microRNA, human
  • MIRN222 microRNA, human
  • MicroRNAs