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dc.contributor.authorUtnes, Peter
dc.contributor.authorLøkke, Cecilie
dc.contributor.authorFlægstad, Trond
dc.contributor.authorEinvik, Christer
dc.date.accessioned2019-10-25T11:06:07Z
dc.date.available2019-10-25T11:06:07Z
dc.date.issued2019-03-11
dc.description.abstractNeuroblastoma is a pediatric cancer of the developing sympathetic nervous system. High-risk neuroblastoma patients typically undergo an initial remission in response to treatment, followed by recurrence of aggressive tumors that have become refractory to further treatment. The need for biomarkers that can select patients not responding well to therapy in an early phase is therefore needed. In this study, we used next generation sequencing technology to determine the expression profiles in high-risk neuroblastoma cell lines established before and after therapy. Using partial least squares-discriminant analysis (PLS-DA) with least absolute shrinkage and selection operator (LASSO) and leave-one-out cross-validation, we identified a panel of 55 messenger RNAs and 17 long non-coding RNAs (lncRNAs) which were significantly altered in the expression between cell lines isolated from primary and recurrent tumors. From a neuroblastoma patient cohort, we found 20 of the 55 protein-coding genes to be differentially expressed in patients with unfavorable compared with favorable outcome. We further found a twofold increase or decrease in hazard ratios in these genes when comparing patients with unfavorable and favorable outcome. Gene set enrichment analysis (GSEA) revealed that these genes were involved in proliferation, differentiation and regulated by Polycomb group (PcG) proteins. Of the 17 lncRNAs, 3 upregulated (<i>NEAT1, SH3BP5-AS1, NORAD</i>) and 3 downregulated lncRNAs (<i>DUBR, MEG3, DHRS4-AS1</i>) were also found to be differentially expressed in favorable compared with unfavorable outcome. Moreover, using expression profiles on both miRNAs and mRNAs in the same cohort of cell lines, we found 13 downregulated and 18 upregulated experimentally observed miRNA target genes targeted by <i>miR-21, -424</i> and <i>-30e, -29b, -138, -494, -181a, -34a, -29b</i>, respectively. The advantage of analyzing biomarkers in a clinically relevant neuroblastoma model system enables further studies on the effect of individual genes upon gene perturbation. In summary, this study identified several genes, which may aid in the prediction of response to therapy and tumor recurrence.en_US
dc.descriptionSource at <a href=https://doi.org/10.1177/1176935119832910>https://doi.org/10.1177/1176935119832910</a>.en_US
dc.identifier.citationUtnes, P., Løkke, C., Flægstad, T. & Einvik, C. (2019). Clinically Relevant Biomarker Discovery in High-Risk Recurrent Neuroblastoma. <i>Cancer Informatics, 18</i>, 1-16. https://doi.org/10.1177%2F1176935119832910en_US
dc.identifier.cristinIDFRIDAID 1732443
dc.identifier.doi10.1177/1176935119832910
dc.identifier.issn1176-9351
dc.identifier.urihttps://hdl.handle.net/10037/16474
dc.language.isoengen_US
dc.publisherSageen_US
dc.relation.journalCancer Informatics
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762en_US
dc.subjectneuroblastomaen_US
dc.subjecthigh risken_US
dc.subjecttumor recurrenceen_US
dc.subjectbiomarker discoveryen_US
dc.subjectnext generation sequencingen_US
dc.subjectmiRNAen_US
dc.subjectlncRNAen_US
dc.titleClinically Relevant Biomarker Discovery in High-Risk Recurrent Neuroblastomaen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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