MicroRNAs as predictors for CNS relapse of systemic diffuse large B-cell lymphoma

Nir Pillar, Osnat Bairey, Neta Goldschmidt, Yakov Fellig, Yevgenia Rosenblat, Itchak Shehtman, Danielle Haguel, Pia Raanani, Noam Shomron, Tali Siegal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Systemic diffuse large B-cell lymphoma (DLBCL) is a potentially curable disease using current regimen of immunochemotherapy. Central nervous system (CNS) relapse is a complication that occurs in approximately 5% of DLBCL patients and is associated with a high fatality rate. Early identification of molecular markers for CNS involvement may serve for the highly needed accurate stratification of patients into risk groups regarding CNS relapse. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level and are known to be involved in DLBCL pathophysiology. In this study, we utilized miRNA multiplex reading of systemic newly diagnosed DLBCL samples obtained from patients with clinical risk factors for CNS involvement whose disease course was distinguished by the presence or absence of subsequent CNS relapse. The analysis detected two differentially expressed miRNAs, miR-20a and miR-30d, that predict for CNS involvement. Replication of these results in different samples was used for validation. We performed bioinformatics miRNA-target enrichment analysis to reveal a number of putative mechanisms for these miRNAs regulation of CNS relapse, including neuronal plasticity and WNT signaling pathway. Altogether, we show that the expression level of two miRNAs may have valuable information that may refine stratification for patients-at-risk for relapse with CNS involvement in DLBCL. Further larger scale studies are needed to shed light on the pathways involved in this disease.

Original languageEnglish
Pages (from-to)86020-86030
Number of pages11
JournalOncotarget
Volume8
Issue number49
DOIs
StatePublished - 17 Oct 2017

Funding

FundersFunder number
Adelis Foundation
CBRN
Consortium for Mapping Retinal Degeneration Disorders in Israel
Faculty of Medicine grants of Tel-Aviv University
Israeli Ministry of Science
Kateznik K. Association Holocaust
Lirot’ Association
Office of Assistant Minister of Defense for Chemical
Saban Family Foundation
Israel Cancer Research Fund
Melanoma Research Alliance
Center for Outcomes Research and Evaluation, Yale School of Medicine1852/16
Margot Marsh Biodiversity Foundation
Foundation Fighting Blindness
United States-Israel Binational Science Foundation
Israel Cancer Association
Israel Science Foundation41/11
Tel Aviv University
Israeli Centers for Research Excellence
Ministry of Defense
Wolfson Family Charitable Trust

    Keywords

    • CNS relapse prediction
    • MiR-20a
    • MiR-30d
    • MicroRNA
    • Systemic DLBCL

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