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Integrative multi-omics reveals two biologically distinct groups of pilocytic astrocytoma

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dc.contributor.authorPicard, Daniel
dc.contributor.authorFelsberg, Jörg
dc.contributor.authorLangini, Maike
dc.contributor.authorStachura, Paweł
dc.contributor.authorQin, Nan
dc.contributor.authorMacas, Jadranka
dc.contributor.authorReiss, Yvonne
dc.contributor.authorBartl, Jasmin
dc.contributor.authorSelt, Florian
dc.contributor.authorSigaud, Romain
dc.contributor.authorMeyer, Frauke-D.
dc.contributor.authorStefanski, Anja
dc.contributor.authorStühler, Kai
dc.contributor.authorRoque, Lucia
dc.contributor.authorRoque, Rafael
dc.contributor.authorPandyra, Aleksandra A.
dc.contributor.authorBrozou, Triantafyllia
dc.contributor.authorKnobbe-Thomsen, Christiane
dc.contributor.authorPlate, Karl H.
dc.contributor.authorRoesch, Alexander
dc.contributor.authorMilde, Till
dc.contributor.authorReifenberger, Guido
dc.contributor.authorLeprivier, Gabriel
dc.contributor.authorFaria, Claudia
dc.contributor.authorRemke, Marc
dc.date.accessioned2023-09-12T12:51:21Z
dc.date.available2023-09-12T12:51:21Z
dc.date.issued2023
dc.description© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.pt_PT
dc.description.abstractPilocytic astrocytoma (PA), the most common pediatric brain tumor, is driven by aberrant mitogen-activated protein kinase signaling most commonly caused by BRAF gene fusions or activating mutations. While 5-year overall survival rates exceed 95%, tumor recurrence or progression constitutes a major clinical challenge in incompletely resected tumors. Here, we used similarity network fusion (SNF) analysis in an integrative multi-omics approach employing RNA transcriptomic and mass spectrometry-based proteomic profiling to molecularly characterize PA tissue samples from 62 patients. Thereby, we uncovered that PAs segregated into two molecularly distinct groups, namely, Group 1 and Group 2, which were validated in three non-overlapping cohorts. Patients with Group 1 tumors were significantly younger and showed worse progression-free survival compared to patients with group 2 tumors. Ingenuity pathways analysis (IPA) and gene set enrichment analysis (GSEA) revealed that Group 1 tumors were enriched for immune response pathways, such as interferon signaling, while Group 2 tumors showed enrichment for action potential and neurotransmitter signaling pathways. Analysis of immune cell-related gene signatures showed an enrichment of infiltrating T Cells in Group 1 versus Group 2 tumors. Taken together, integrative multi-omics of PA identified biologically distinct and prognostically relevant tumor groups that may improve risk stratification of this single pathway driven tumor type.pt_PT
dc.description.sponsorshipThis project funded in part by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project-ID 418179183—KFO 337, RO 3577/7-1 (A.R.), RE 2857/4-1 (M.R.) and supported by Biomed Valley and Day One Therapeutics (T.M.), Fundação Amélia de Melo (C.C.F.) and Fundação Millennium bcp (C.C.F.)pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationActa Neuropathol. 2023 Sep 1pt_PT
dc.identifier.doi10.1007/s00401-023-02626-5pt_PT
dc.identifier.eissn1432-0533
dc.identifier.issn0001-6322
dc.identifier.urihttp://hdl.handle.net/10451/59227
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relation.publisherversionhttps://www.springer.com/journal/401pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectIntegrative multi-omicspt_PT
dc.subjectIntertumoral heterogeneitypt_PT
dc.subjectPilocytic astrocytomapt_PT
dc.titleIntegrative multi-omics reveals two biologically distinct groups of pilocytic astrocytomapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.titleActa Neuropathologicapt_PT
person.familyNameValente Fidalgo Ramos Roque
person.familyNameFaria
person.givenNameRafael
person.givenNameClaudia
person.identifier.ciencia-id051B-EAEE-FD29
person.identifier.ciencia-idAD1B-C408-B6A8
person.identifier.orcid0000-0003-1259-9922
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicatione26c9129-fea9-4571-bf5a-43305937bf54
relation.isAuthorOfPublication94ff2476-7001-4e97-9396-4a8716a7cbba
relation.isAuthorOfPublication.latestForDiscovery94ff2476-7001-4e97-9396-4a8716a7cbba

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