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Title: A microRNA signature profile in EBV+ diffuse large B-cell lymphoma of the elderly
Authors: Andrade, Tathiana Azevedo de [UNIFESP]
Evangelista, Adriane Feijo
Campos, Antônio Hugo José Fróes Marques
Poles, Wagner Augusto [UNIFESP]
Borges, Natalia Morais [UNIFESP]
Coutinho-Camillo, Claudia Malheiros
Soares, Fernando Augusto
Vassallo, José
Paes, Roberto Pinto
Zerbini, Maria Cláudia Nogueira
Scapulatempo Neto, Cristovam
Alves, Antonio Correa [UNIFESP]
Young, Ken H.
Colleoni, Gisele Wally Braga [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Hosp Canc Barretos
AC Camargo Canc Ctr
Universidade Estadual de Campinas (UNICAMP)
Santa Casa Misericordia Sao Paulo
Universidade de São Paulo (USP)
Univ Texas MD Anderson Canc Ctr
Keywords: DLBCL
Issue Date: 15-Dec-2014
Publisher: Impact Journals Llc
Citation: Oncotarget. Albany: Impact Journals Llc, v. 5, n. 23, p. 11813-11826, 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(+)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.
ISSN: 1949-2553
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