Detail publikace

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

LAZIC, D. KROMP, F. RIFATBEGOVIC, F. REPISCAK, P. KIRR, M. MÍVALT, F. HALBRITTER, F. BERNKOPF, M. BILLECK, A. USSOWICZ, M. AMBROS, I. AMBROS, P. GERNER, C. LADENSTEIN, R. OSTALECKI, C. TASCHNER-MANDL, S.

Originální název

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

Typ

článek v časopise ve Web of Science, Jimp

Jazyk

angličtina

Originální abstrakt

Bone 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.

Klíčová slova

bone marrow;metastatis;neuroblastoma;tumor heterogeneity; tumor microenvironment;sngle-cell analysis;multiplex imaging;deep learning;transcriptomics;disseminated tumor cells

Autoři

LAZIC, D.; KROMP, F.; RIFATBEGOVIC, F.; REPISCAK, P.; KIRR, M.; MÍVALT, F.; HALBRITTER, F.; BERNKOPF, M.; BILLECK, A.; USSOWICZ, M.; AMBROS, I.; AMBROS, P.; GERNER, C.; LADENSTEIN, R.; OSTALECKI, C.; TASCHNER-MANDL, S.

Vydáno

26. 8. 2021

Nakladatel

MDPI

ISSN

2072-6694

Periodikum

Cancers

Ročník

13

Číslo

17

Stát

Švýcarská konfederace

Strany od

1

Strany do

25

Strany počet

25

URL

https://www.mdpi.com/2072-6694/13/17/4311

Plný text v Digitální knihovně

http://hdl.handle.net/11012/201640

BibTex

@article{BUT172424,
  author="Daria {Lazic} and Florian {Kromp} and Fikret {Rifatbegovic} and Peter {Repiscak} and Michael {Kirr} and Filip {Mívalt} and Florian {Halbritter} and Marie {Bernkopf} and Andrea {Billeck} and Marek {Ussowicz} and Inge {Ambros} and Peter {Ambros} and Christopher {Gerner} and Ruth {Ladenstein} and Christian {Ostalecki} and Sabine {Taschner-Mandl}",
  title="Landscape of Bone Marrow Metastasis in Human Neuroblastoma Unraveled by Transcriptomics and Deep Multiplex Imaging",
  journal="Cancers",
  year="2021",
  volume="13",
  number="17",
  pages="1--25",
  doi="10.3390/cancers13174311",
  issn="2072-6694",
  url="https://www.mdpi.com/2072-6694/13/17/4311"
}