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

Author(s):Show less -

de Andrade, Tathiana Azevedo ^[1] ; Evangelista, Adriane Feijo ^[2] ; Froes Campos, Antonio Hugo ^[3] ; Poles, Wagner Augusto ^[1] ; Borges, Natalia Morais ^[1] ; Coutinho Camillo, Claudia Malheiros ^[3] ; Soares, Fernando Augusto ^[3] ; Vassallo, Jose ^{[4, 3]} ; Paes, Roberto Pinto ^[5] ; Zerbini, Maria Claudia ^[6] ; Scapulatempo, Cristovam ^[2] ; Alves, Antonio Correa ^[1] ; Young, Ken H. ^[7] ; Braga Colleoni, Gisele Wally ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, UNIFESP, Sao Paulo - Brazil

^[2] Hosp Canc Barretos, Barretos - Brazil

^[3] AC Camargo Canc Ctr, Sao Paulo - Brazil

^[4] Univ Estadual Campinas, Campinas, SP - Brazil

^[5] Santa Casa Misericordia Sao Paulo, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Fac Med, Sao Paulo - Brazil

^[7] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 - USA

• Document type: Journal article
• Source: ONCOTARGET; v. 5, n. 23, p. 11813-11826, DEC 15 2014.
• Web of Science Citations: 22

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. (AU)

• FAPESP's process: 10/17668-6 - Identification of biomarkers and possible therapeutical targets in B-cell lymphoproliferative disorders
• Grantee: Gisele Wally Braga Colleoni
• Support Opportunities: Research Projects - Thematic Grants