Publication detail

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.

Original Title

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

Type

journal article in Web of Science

Language

English

Original Abstract

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.

Keywords

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

Authors

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.

Released

26. 8. 2021

Publisher

MDPI

ISBN

2072-6694

Periodical

Cancers

Year of study

13

Number

17

State

Swiss Confederation

Pages from

1

Pages to

25

Pages count

25

URL

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

Full text in the Digital Library

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"
}