Longitudinal evaluation of serum microRNAs as biomarkers for neuroblastoma burden and therapeutic p53 reactivation
- Author
- Alan Van Goethem (UGent) , Jill Deleu (UGent) , Nurten Yigit (UGent) , Celine Everaert (UGent) , Myrthala Moreno-Smith, Sanjeev A Vasudevan, Fjoralba Zeka (UGent) , Fleur Demuynck (UGent) , Eveline Barbieri, Franki Speleman (UGent) , Pieter Mestdagh (UGent) , Jason Shohet, Jo Vandesompele (UGent) and Tom Van Maerken (UGent)
- Organization
- Project
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- Therapy response monitoring in pediatric cancer basket trial patients
- Exploring the use of extracellular RNA in liquid biopsies for precision oncology purposes
- Therapeutic restoration of p53 function in neuroblastoma
- Preclinical evaluation of the nutlin molecule RG7112 in neuroblastoma
- Identification and functional characterisation of non-coding RNAs in cancer
- Abstract
- Accurate assessment of treatment response and residual disease is indispensable for the evaluation of cancer treatment efficacy. However, performing tissue biopsies for longitudinal follow-up poses a major challenge in the management of solid tumours like neuroblastoma. In the present study, we evaluated whether circulating miRNAs are suitable to monitor neuroblastoma tumour burden and whether treatment-induced changes of miRNA abundance in the tumour are detectable in serum. We performed small RNA sequencing on longitudinally collected serum samples from mice carrying orthotopic neuroblastoma xenografts that were exposed to treatment with idasanutlin or temsirolimus. We identified 57 serum miRNAs to be differentially expressed upon xenograft tumour manifestation, out of which 21 were also found specifically expressed in the serum of human high-risk neuroblastoma patients. The murine serum levels of these 57 miRNAs correlated with tumour tissue expression and tumour volume, suggesting potential utility for monitoring tumour burden. In addition, we describe serum miRNAs that dynamically respond to p53 activation following treatment of engrafted mice with idasanutlin. We identified idasanutlin-induced serum miRNA expression changes upon one day and 11 days of treatment. By limiting to miRNAs with a tumour-related induction, we put forward hsa-miR-34a-5p as a potential pharmacodynamic biomarker of p53 activation in serum.
- Keywords
- General Medicine, MDM2 ANTAGONIST, TUMOR-SUPPRESSOR, PRECLINICAL EVALUATION, RISK STRATIFICATION, DNA, EXPRESSION, PATHWAY, DIFFERENTIATION, HETEROGENEITY, TEMOZOLOMIDE
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01GQ4PZYZ4ZEY4134GJ5CEX40T
- MLA
- Van Goethem, Alan, et al. “Longitudinal Evaluation of Serum MicroRNAs as Biomarkers for Neuroblastoma Burden and Therapeutic P53 Reactivation.” NAR CANCER, vol. 5, no. 1, Oxford University Press (OUP), 2023, doi:10.1093/narcan/zcad002.
- APA
- Van Goethem, A., Deleu, J., Yigit, N., Everaert, C., Moreno-Smith, M., Vasudevan, S. A., … Van Maerken, T. (2023). Longitudinal evaluation of serum microRNAs as biomarkers for neuroblastoma burden and therapeutic p53 reactivation. NAR CANCER, 5(1). https://doi.org/10.1093/narcan/zcad002
- Chicago author-date
- Van Goethem, Alan, Jill Deleu, Nurten Yigit, Celine Everaert, Myrthala Moreno-Smith, Sanjeev A Vasudevan, Fjoralba Zeka, et al. 2023. “Longitudinal Evaluation of Serum MicroRNAs as Biomarkers for Neuroblastoma Burden and Therapeutic P53 Reactivation.” NAR CANCER 5 (1). https://doi.org/10.1093/narcan/zcad002.
- Chicago author-date (all authors)
- Van Goethem, Alan, Jill Deleu, Nurten Yigit, Celine Everaert, Myrthala Moreno-Smith, Sanjeev A Vasudevan, Fjoralba Zeka, Fleur Demuynck, Eveline Barbieri, Franki Speleman, Pieter Mestdagh, Jason Shohet, Jo Vandesompele, and Tom Van Maerken. 2023. “Longitudinal Evaluation of Serum MicroRNAs as Biomarkers for Neuroblastoma Burden and Therapeutic P53 Reactivation.” NAR CANCER 5 (1). doi:10.1093/narcan/zcad002.
- Vancouver
- 1.Van Goethem A, Deleu J, Yigit N, Everaert C, Moreno-Smith M, Vasudevan SA, et al. Longitudinal evaluation of serum microRNAs as biomarkers for neuroblastoma burden and therapeutic p53 reactivation. NAR CANCER. 2023;5(1).
- IEEE
- [1]A. Van Goethem et al., “Longitudinal evaluation of serum microRNAs as biomarkers for neuroblastoma burden and therapeutic p53 reactivation,” NAR CANCER, vol. 5, no. 1, 2023.
@article{01GQ4PZYZ4ZEY4134GJ5CEX40T,
abstract = {{Accurate assessment of treatment response and residual disease is indispensable for the evaluation of cancer treatment efficacy. However, performing tissue biopsies for longitudinal follow-up poses a major challenge in the management of solid tumours like neuroblastoma. In the present study, we evaluated whether circulating miRNAs are suitable to monitor neuroblastoma tumour burden and whether treatment-induced changes of miRNA abundance in the tumour are detectable in serum. We performed small RNA sequencing on longitudinally collected serum samples from mice carrying orthotopic neuroblastoma xenografts that were exposed to treatment with idasanutlin or temsirolimus. We identified 57 serum miRNAs to be differentially expressed upon xenograft tumour manifestation, out of which 21 were also found specifically expressed in the serum of human high-risk neuroblastoma patients. The murine serum levels of these 57 miRNAs correlated with tumour tissue expression and tumour volume, suggesting potential utility for monitoring tumour burden. In addition, we describe serum miRNAs that dynamically respond to p53 activation following treatment of engrafted mice with idasanutlin. We identified idasanutlin-induced serum miRNA expression changes upon one day and 11 days of treatment. By limiting to miRNAs with a tumour-related induction, we put forward hsa-miR-34a-5p as a potential pharmacodynamic biomarker of p53 activation in serum.}},
articleno = {{zcad002}},
author = {{Van Goethem, Alan and Deleu, Jill and Yigit, Nurten and Everaert, Celine and Moreno-Smith, Myrthala and Vasudevan, Sanjeev A and Zeka, Fjoralba and Demuynck, Fleur and Barbieri, Eveline and Speleman, Franki and Mestdagh, Pieter and Shohet, Jason and Vandesompele, Jo and Van Maerken, Tom}},
issn = {{2632-8674}},
journal = {{NAR CANCER}},
keywords = {{General Medicine,MDM2 ANTAGONIST,TUMOR-SUPPRESSOR,PRECLINICAL EVALUATION,RISK STRATIFICATION,DNA,EXPRESSION,PATHWAY,DIFFERENTIATION,HETEROGENEITY,TEMOZOLOMIDE}},
language = {{eng}},
number = {{1}},
pages = {{12}},
publisher = {{Oxford University Press (OUP)}},
title = {{Longitudinal evaluation of serum microRNAs as biomarkers for neuroblastoma burden and therapeutic p53 reactivation}},
url = {{http://doi.org/10.1093/narcan/zcad002}},
volume = {{5}},
year = {{2023}},
}
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