Language
English
Publication Date
3-1-2023
Journal
NAR Cancer
DOI
10.1093/narcan/zcad002
PMID
36683916
PMCID
PMC9846426
PubMedCentral® Posted Date
1-18-2023
PubMedCentral® Full Text Version
Post-print
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.
Published Open-Access
yes
Recommended Citation
Van Goethem, Alan; Deleu, Jill; Yigit, Nurten; et al., "Longitudinal Evaluation of Serum microRNAs as Biomarkers for Neuroblastoma Burden and Therapeutic p53 Reactivation" (2023). Faculty, Staff and Students Publications. 6302.
https://digitalcommons.library.tmc.edu/baylor_docs/6302
Graphical Abstract