Landscape of Bone Marrow Metastasis in Human Neuroblastoma Unraveled by Transcriptomics and Deep Multiplex Imaging

Simple item page
dc.contributor.authorLazic, Dariacs
dc.contributor.authorKromp, Floriancs
dc.contributor.authorRifatbegovic, Fikretcs
dc.contributor.authorRepiscak, Petercs
dc.contributor.authorKirr, Michaelcs
dc.contributor.authorMívalt, Filipcs
dc.contributor.authorHalbritter, Floriancs
dc.contributor.authorBernkopf, Mariecs
dc.contributor.authorBilleck, Andreacs
dc.contributor.authorUssowicz, Marekcs
dc.contributor.authorAmbros, Ingecs
dc.contributor.authorAmbros, Petercs
dc.contributor.authorGerner, Christophercs
dc.contributor.authorLadenstein, Ruthcs
dc.contributor.authorOstalecki, Christiancs
dc.contributor.authorTaschner-Mandl, Sabinecs
dc.coverage.issue17cs
dc.coverage.volume13cs
dc.date.issued2021-08-26cs
dc.description.abstractBone marrow metastasis frequently occurs in patients with solid cancers and most often leads to poor outcome. Yet, the composition of bone marrow metastases, including tumor and surrounding cells, has so far not been characterized. Herein, we aimed to investigate the diversity of tumor and surrounding cells, i.e., the microenvironment, in bone marrow metastases, using the childhood tumor neuroblastoma as a model. To this end, we screened genome-wide datasets to define a panel of cell-specific markers for multiplex microscopy of metastatic bone marrow samples, and developed DeepFLEX, a computational pipeline for subsequent image analysis. Thereby, we identified 35,000 single cells covering metastasized tumor cells, and various types of developing immune and bone marrow cells. In parallel, we analyzed the transcriptome, i.e., all genes that are expressed as mRNA, of 38 patients with and without bone marrow metastasis. We found vast tumor cell diversity and identified a marker protein, FAIM2, which can help to identify a broader range of tumor cell variants. In addition we showed that tumor cell metastasis in the bone marrow is associated with an immune response resembling inflammation, and the presence of cells that can repress an immune attack against cancer cells. Our study suggests that metastatic tumor cells are shaping the bone marrow microenvironment and builds the basis to further investigate its clinical relevance.en
dc.formattextcs
dc.format.extent1-25cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationCancers. 2021, vol. 13, issue 17, p. 1-25.en
dc.identifier.doi10.3390/cancers13174311cs
dc.identifier.issn2072-6694cs
dc.identifier.orcid0000-0002-0693-9495cs
dc.identifier.other172424cs
dc.identifier.researcheridAAX-1872-2021cs
dc.identifier.scopus57205062706cs
dc.identifier.urihttp://hdl.handle.net/11012/201640
dc.language.isoencs
dc.publisherMDPIcs
dc.relation.ispartofCancerscs
dc.relation.urihttps://www.mdpi.com/2072-6694/13/17/4311cs
dc.rightsCreative Commons Attribution 4.0 Internationalcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/2072-6694/cs
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/cs
dc.subjectbone marrowen
dc.subjectmetastatisen
dc.subjectneuroblastomaen
dc.subjecttumor heterogeneityen
dc.subjecttumor microenvironmenten
dc.subjectsngle-cell analysisen
dc.subjectmultiplex imagingen
dc.subjectdeep learningen
dc.subjecttranscriptomicsen
dc.subjectdisseminated tumor cellsen
dc.titleLandscape of Bone Marrow Metastasis in Human Neuroblastoma Unraveled by Transcriptomics and Deep Multiplex Imagingen
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-172424en
sync.item.dbtypeVAVen
sync.item.insts2025.02.03 15:39:49en
sync.item.modts2025.01.17 16:36:53en
thesis.grantorVysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií. Ústav biomedicínského inženýrstvícs
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
cancers1304311v2.pdf
Size:
4.39 MB
Format:
Adobe Portable Document Format
Description:
cancers1304311v2.pdf
Download
Collections
Ústav biomedicínského inženýrství