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dc.contributor.authorCui, Qingyan
dc.contributor.authorVari, Frank
dc.contributor.authorCristino, Alexandre S
dc.contributor.authorSalomon, Carlos
dc.contributor.authorRice, Gregory E
dc.contributor.authorSabdia, Muhammed B
dc.contributor.authorGuanzon, Dominic
dc.contributor.authorPalma, Carlos
dc.contributor.authorMathew, Marina
dc.contributor.authorTalaulikar, Dipti
dc.contributor.authorJain, Sanjiv
dc.contributor.authorHan, Erica
dc.contributor.authorHertzberg, Mark S
dc.contributor.authorGould, Clare
dc.contributor.authorCrooks, Pauline
dc.contributor.authorThillaiyampalam, Gayathri
dc.contributor.authorKeane, Colm
dc.contributor.authorGandhi, Maher K
dc.date.accessioned2020-02-17T04:35:28Z
dc.date.available2020-02-17T04:35:28Z
dc.date.issued2018
dc.identifier.issn1949-2553
dc.identifier.doi10.18632/oncotarget.26141
dc.identifier.urihttp://hdl.handle.net/10072/391595
dc.description.abstractMicroRNA (miRNA)s are dysregulated in Diffuse large B-cell lymphoma (DLBCL), where they reflect the malignant B-cells and the immune infiltrate within the tumor microenvironment. There remains a paucity of data in DLBCL regarding cell-free (c-f) miRNA as disease response biomarkers. Immunosuppressive monocyte/macrophages, which are enriched in DLBCL, are disease response markers in DLBCL, with miRNA key regulators of their immunosuppressive function. Our aim was to determine whether plasma miRNA that reflect the activity of the malignant B-cell and/or immunosuppressive monocytes/macrophages, have value as minimally-invasive disease response biomarkers in DLBCL. Quantification of 99 DLBCL tissues, to select miRNA implicated in immunosuppressive monocytes/macrophage biology, found miR-494 differentially elevated. In a discovery cohort (22 patients), pre-therapy c-f miR-494 and miR-21 but not miR-155 were raised relative to healthy plasma. Both miR-494 and miR-21 levels 3-6 months reduced post immuno-chemotherapy. The validation cohort (56 patients) was from a prospective clinical trial. Interestingly, in sequential samples both miRNAs decreased in patients becoming Positron Emission Tomography/Computerized Tomography (PET/CT)-ve, but not in those remaining interim-PET/CT+. Patient monocytes were phenotypically and functionally immunosuppressive with ex-vivo monocyte depletion enhancing T-cell proliferation in patient but not healthy samples. Pre-therapy monocytes showed an immunosuppressive transcriptome and raised levels of miR-494. MiR-494 was present in all c-f nanoparticle fractions but was most readily detectable in unfractionated plasma. Circulating c-f miR-494 and miR-21 are disease response biomarkers with differential response stratified by interim-PET/CT in patients with DLBCL. Further studies are required to explore their manipulation as potential therapeutic targets.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherImpact Journals, LLC
dc.relation.ispartofpagefrom34644
dc.relation.ispartofpageto34657
dc.relation.ispartofissue78
dc.relation.ispartofjournalOncotarget
dc.relation.ispartofvolume9
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchcode3211
dc.subject.keywordsbiomarker
dc.subject.keywordsdiffuse large B-cell lymphoma
dc.subject.keywordsmiRNA-21
dc.subject.keywordsmiRNA-494
dc.subject.keywordspositron emission tomography
dc.titleCirculating cell-free miR-494 and miR-21 are disease response biomarkers associated with interim-positron emission tomography response in patients with diffuse large B-cell lymphoma
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationCui, Q; Vari, F; Cristino, AS; Salomon, C; Rice, GE; Sabdia, MB; Guanzon, D; Palma, C; Mathew, M; Talaulikar, D; Jain, S; Han, E; Hertzberg, MS; Gould, C; Crooks, P; Thillaiyampalam, G; Keane, C; Gandhi, MK, Circulating cell-free miR-494 and miR-21 are disease response biomarkers associated with interim-positron emission tomography response in patients with diffuse large B-cell lymphoma., Oncotarget, 2018, 9 (78), pp. 34644-34657
dcterms.dateAccepted2018-09-08
dcterms.licensehttps://creativecommons.org/licenses/by/3.0/
dc.date.updated2020-02-17T04:33:11Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© Cui et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
gro.hasfulltextFull Text
gro.griffith.authorThillaiyampalam, Gayathri
gro.griffith.authorCristino, Alex


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