Oncotarget

Research Papers: Gerotarget (Focus on Aging):

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

Tathiana Azevedo de Andrade _, Adriane Feijo Evangelista, Antonio Hugo Froes Campos, Wagner Augusto Poles, Natalia Morais Borges, Claudia Malheiros Coutinho Camillo, Fernando Augusto Soares, Jose Vassallo, Roberto Pinto Paes, Maria Claudia Zerbini, Cristovam Scapulatempo, Antonio Correa Alves, Ken H. Young and Gisele Wally Braga Colleoni

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Oncotarget. 2014; 5:11813-11826. https://doi.org/10.18632/oncotarget.2952

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Abstract

Tathiana Azevedo de Andrade1, Adriane Feijo Evangelista2, Antonio Hugo Froes Campos3, Wagner Augusto Poles1, Natalia Morais Borges1, Claudia Malheiros Coutinho Camillo3, Fernando Augusto Soares3, Jose Vassallo3,4, Roberto Pinto Paes5, Maria Claudia Zerbini6, Cristovam Scapulatempo2, Antonio Correa Alves1, Ken H. Young7,* and Gisele Wally Braga Colleoni1,*

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.


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