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Head and Neck Squamous Cell Carcinoma Biopsies Maintained Ex Vivo on a Perfusion Device Show Gene Changes with Time and Clinically Relevant Doses of Irradiation

Green, Victoria; Baldwin, Lydia; England, James; Marshall, Gayle; Frost, Lucy; Moore, Craig; Greenman, John

Authors

Lydia Baldwin

James England

Gayle Marshall

Lucy Frost

Craig Moore



Abstract

Advancements in 3-Dimensional (3D) culture models for studying disease have increased significantly over the last two decades, but fully understanding how these models represent in vivo still requires further investigation. The current study investigated differences in gene expression between a baseline sample and that maintained on a tissue-on-chip perfusion device for up to 96 h, with and without clinically-relevant doses of irradiation, to allow differentiation of model and treatment effects. Tumour tissue samples from 7 Head and Neck Squamous Cell Carcinomas (HNSCC) patients were sub-divided and either fixed immediately upon excision or maintained in a tissue-on-chip device for 48 and 96 h, with or without 2 Gray (Gy) or 10 Gy irradiation. Gene expression was measured using an nCounter® PanCancer Progression Panel. Differentially expressed genes between pre- and post-ex vivo culture, and control and irradiated samples were identified using nSolver software (version 4.0). The secretome from the tumour-on-chip was analysed for the presence of cytokines using a Proteome Profiler™ platform. Significant numbers of genes both increased (n = 6 and 64) and decreased (n = 18 and 58) in expression in the tissue maintained on-chip for 48 and 96 h, respectively, compared to fresh tissue; however, the irradiation schedule chosen did not induce significant changes in gene expression or cytokine secretion. Although HNSCC tissue maintained ex vivo shows a decrease in a large proportion of altered genes, 25% and 53% (48 and 96 h) do show increased expression, suggesting that the tissue remains functional. Irradiation of tumour tissue-on-chip needs to be conducted for longer time periods for specific gene changes to be observed, but we have shown, for the first time, the feasibility of using this perfusion platform for studying the genomic response of HNSCC tissue biopsies.

Citation

Green, V., Baldwin, L., England, J., Marshall, G., Frost, L., Moore, C., & Greenman, J. (2023). Head and Neck Squamous Cell Carcinoma Biopsies Maintained Ex Vivo on a Perfusion Device Show Gene Changes with Time and Clinically Relevant Doses of Irradiation. Cancers, 15(18), Article 4575. https://doi.org/10.3390/cancers15184575

Journal Article Type Article
Acceptance Date Sep 11, 2023
Online Publication Date Sep 15, 2023
Publication Date Sep 2, 2023
Deposit Date Sep 25, 2023
Publicly Available Date Sep 26, 2023
Journal Cancers
Electronic ISSN 2072-6694
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 15
Issue 18
Article Number 4575
DOI https://doi.org/10.3390/cancers15184575
Keywords HNSCC; Perfusion; Nanostring; Biomarker; Irradiation treatment
Public URL https://hull-repository.worktribe.com/output/4398552

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0

Copyright Statement
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).




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