Screening for prognostic microRNAs associated with treatment failure in diffuse large B cell lymphoma
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- dc.contributor.author Bento, Leyre
- dc.contributor.author Vögler, Oliver
- dc.contributor.author Sas-Barbeito, Adriana
- dc.contributor.author Muncunill, Josep
- dc.contributor.author Ros, Teresa
- dc.contributor.author Martínez, Jordi
- dc.contributor.author Quintero-Duarte, Adriana
- dc.contributor.author Ramos, Rafel
- dc.contributor.author Asensio, Víctor Jose
- dc.contributor.author Fernández Rodríguez, M. Concepción
- dc.contributor.author Salar Silvestre, Antonio
- dc.contributor.author Navarro, Alfons
- dc.contributor.author Del Campo, Raquel
- dc.contributor.author Ibarra, Javier
- dc.contributor.author Alemany, Regina
- dc.contributor.author Gutiérrez, Antonio
- dc.date.accessioned 2022-08-03T15:38:58Z
- dc.date.available 2022-08-03T15:38:58Z
- dc.date.issued 2022
- dc.description.abstract Diffuse large B cell lymphoma (DLBCL) treatment with R-CHOP regimen produces 5-year progression-free survival and overall survival of around 60-70%. Our objective was to discover prognostic biomarkers allowing early detection of the remaining 30-40% with poor long-term outcome. For this purpose, we applied a novel strategy: from a cohort of DLBCL patients, treated with standard therapy, a discovery group of 12 patients with poor prognosis (advanced stage III-IV, R-IPI > 2) was formed, consisting of six chemoresistant (refractory/early relapse < 12 months) and six chemosensitive (complete remission > 3 years) subjects. By using microarray assays, the most differentially expressed miRNAs were defined as an initial set of prognostic miRNA candidates. Their expression was then analyzed in a validation cohort of 68 patients and the three miRNAs with the most significant impact on event-free and overall survival were selected. In the DLBCL cell line U-2932 the transfection with miR-1244 and miR-193b-5p, but not miR-1231, blocked the effect of CHOP on cell viability. A subsequent gene set enrichment analysis in patients revealed the implication of the first two miRNAs in cell cycle control and chemoresistance-related pathways, whereas the last one was involved in immunological processes. In conclusion, this novel strategy identified three promising prognostic markers for DLBCL patients at high risk of failure with standard therapy.
- dc.format.mimetype application/pdf
- dc.identifier.citation Bento L, Vögler O, Sas-Barbeito A, Muncunill J, Ros T, Martínez J, Quintero-Duarte A, Ramos R, Asensio VJ, Fernández-Rodríguez C, Salar A, Navarro A, Del Campo R, Ibarra J, Alemany R, Gutiérrez A. Screening for prognostic microRNAs associated with treatment failure in diffuse large B cell lymphoma. Cancers (Basel). 2022 Feb 20;14(4):1065. DOI: 10.3390/cancers14041065
- dc.identifier.doi http://dx.doi.org/10.3390/cancers14041065
- dc.identifier.issn 2072-6694
- dc.identifier.uri http://hdl.handle.net/10230/53919
- dc.language.iso eng
- dc.publisher MDPI
- dc.relation.ispartof Cancers (Basel). 2022 Feb 20;14(4):1065
- dc.rights © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Chemoresistance
- dc.subject.keyword Diffuse large B cell lymphoma
- dc.subject.keyword Epigenetic markers
- dc.subject.keyword MicroRNA
- dc.subject.keyword Prognosis
- dc.title Screening for prognostic microRNAs associated with treatment failure in diffuse large B cell lymphoma
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion