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Whole transcriptome profiling of liquid biopsies from tumour xenografted mouse models enables specific monitoring of tumour-derived extracellular RNA

Vanessa Vermeirssen (UGent) , Jill Deleu (UGent) , Annelien Morlion (UGent) , Celine Everaert (UGent) , Jilke De Wilde (UGent) , Jasper Anckaert (UGent) , Kaat Durinck (UGent) , Justine Nuytens (UGent) , Muhammad Rishfi (UGent) , Franki Speleman (UGent) , et al.
(2022) NAR CANCER. 4(4).
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Abstract
While cell-free DNA (cfDNA) is widely being investigated, free circulating RNA (extracellular RNA, exRNA) has the potential to improve cancer therapy response monitoring and detection due to its dynamic nature. However, it remains unclear in which blood subcompartment tumour-derived exRNAs primarily reside. We developed a host-xenograft deconvolution framework, exRNAxeno, with mapping strategies to either a combined human-mouse reference genome or both species genomes in parallel, applicable to exRNA sequencing data from liquid biopsies of human xenograftmousemodels. The tool enables to distinguish (human) tumoural RNA from (murine) host RNA, to specifically analyse tumour-derived exRNA. We applied the combined pipeline to total exRNA sequencing data from 95 blood-derived liquid biopsy samples from 30 mice, xenografted with 11 different tumours. Tumoural exRNA concentrations are not determined by plasma platelet levels, while host exRNA concentrations increase with platelet content. Furthermore, a large variability in exRNA abundance and transcript content across individual mice is observed. The tumoural gene detectability in plasma is largely correlated with the RNA expression levels in the tumour tissue or cell line. These findings unravel new aspects of tumour-derived exRNA biology in xenograftmodels and open new avenues to further investigate the role of exRNA in cancer.
Keywords
CANCER, PDX

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MLA
Vermeirssen, Vanessa, et al. “Whole Transcriptome Profiling of Liquid Biopsies from Tumour Xenografted Mouse Models Enables Specific Monitoring of Tumour-Derived Extracellular RNA.” NAR CANCER, vol. 4, no. 4, 2022, doi:10.1093/narcan/zcac037.
APA
Vermeirssen, V., Deleu, J., Morlion, A., Everaert, C., De Wilde, J., Anckaert, J., … Decock, A. (2022). Whole transcriptome profiling of liquid biopsies from tumour xenografted mouse models enables specific monitoring of tumour-derived extracellular RNA. NAR CANCER, 4(4). https://doi.org/10.1093/narcan/zcac037
Chicago author-date
Vermeirssen, Vanessa, Jill Deleu, Annelien Morlion, Celine Everaert, Jilke De Wilde, Jasper Anckaert, Kaat Durinck, et al. 2022. “Whole Transcriptome Profiling of Liquid Biopsies from Tumour Xenografted Mouse Models Enables Specific Monitoring of Tumour-Derived Extracellular RNA.” NAR CANCER 4 (4). https://doi.org/10.1093/narcan/zcac037.
Chicago author-date (all authors)
Vermeirssen, Vanessa, Jill Deleu, Annelien Morlion, Celine Everaert, Jilke De Wilde, Jasper Anckaert, Kaat Durinck, Justine Nuytens, Muhammad Rishfi, Franki Speleman, Hanne Van Droogenbroeck, Kimberly Verniers, MF Baietti, M Albersen, E Leucci, E Post, MG Best, Tom Van Maerken, Bram De Wilde, Jo Vandesompele, and Anneleen Decock. 2022. “Whole Transcriptome Profiling of Liquid Biopsies from Tumour Xenografted Mouse Models Enables Specific Monitoring of Tumour-Derived Extracellular RNA.” NAR CANCER 4 (4). doi:10.1093/narcan/zcac037.
Vancouver
1.
Vermeirssen V, Deleu J, Morlion A, Everaert C, De Wilde J, Anckaert J, et al. Whole transcriptome profiling of liquid biopsies from tumour xenografted mouse models enables specific monitoring of tumour-derived extracellular RNA. NAR CANCER. 2022;4(4).
IEEE
[1]
V. Vermeirssen et al., “Whole transcriptome profiling of liquid biopsies from tumour xenografted mouse models enables specific monitoring of tumour-derived extracellular RNA,” NAR CANCER, vol. 4, no. 4, 2022.
@article{01GKHPA0K5M1ZCKX0SZQ83DB3D,
  abstract     = {{While cell-free DNA (cfDNA) is widely being investigated, free circulating RNA (extracellular RNA, exRNA) has the potential to improve cancer therapy response monitoring and detection due to its dynamic nature. However, it remains unclear in which blood subcompartment tumour-derived exRNAs primarily reside. We developed a host-xenograft deconvolution framework, exRNAxeno, with mapping strategies to either a combined human-mouse reference genome or both species genomes in parallel, applicable to exRNA sequencing data from liquid biopsies of human xenograftmousemodels. The tool enables to distinguish (human) tumoural RNA from (murine) host RNA, to specifically analyse tumour-derived exRNA. We applied the combined pipeline to total exRNA sequencing data from 95 blood-derived liquid biopsy samples from 30 mice, xenografted with 11 different tumours. Tumoural exRNA concentrations are not determined by plasma platelet levels, while host exRNA concentrations increase with platelet content. Furthermore, a large variability in exRNA abundance and transcript content across individual mice is observed. The tumoural gene detectability in plasma is largely correlated with the RNA expression levels in the tumour tissue or cell line. These findings unravel new aspects of tumour-derived exRNA biology in xenograftmodels and open new avenues to further investigate the role of exRNA in cancer.}},
  author       = {{Vermeirssen, Vanessa and Deleu, Jill and Morlion, Annelien and Everaert, Celine and De Wilde, Jilke and Anckaert, Jasper and Durinck, Kaat and Nuytens, Justine and Rishfi, Muhammad and Speleman, Franki and Van Droogenbroeck, Hanne and Verniers, Kimberly and Baietti, MF and Albersen, M and Leucci, E and Post, E and Best, MG and Van Maerken, Tom and De Wilde, Bram and Vandesompele, Jo and Decock, Anneleen}},
  issn         = {{2632-8674}},
  journal      = {{NAR CANCER}},
  keywords     = {{CANCER,PDX}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{14}},
  title        = {{Whole transcriptome profiling of liquid biopsies from tumour xenografted mouse models enables specific monitoring of tumour-derived extracellular RNA}},
  url          = {{http://doi.org/10.1093/narcan/zcac037}},
  volume       = {{4}},
  year         = {{2022}},
}

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