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Identification of soluble tissue‑derived biomarkers from human thyroid tissue explants maintained on a microfluidic device

Riley, Andrew; Jones, Heidi; England, James; Kuvshinov, Dmitriy; Green, Victoria; Greenman, John

Authors

Andrew Riley

Heidi Jones

James England

Dmitriy Kuvshinov

Victoria Green



Abstract

Although a large cohort of potential biomarkers for thyroid cancer aggressiveness have been tested in various formats in recent years, to the best of our knowledge, thyro‑ globulin and calcitonin remain the only two established biomarkers associated with thyroid cancer management. Our group has recently validated a novel means of maintaining live, human ex vivo thyroid tissue within a tissue‑on‑chip format. The present pilot study aimed to interrogate the tissue effluent, containing all the soluble markers released by the tissue samples maintained within the devices' tissue chamber, for the presence of markers potentially associated with thyroid cancer aggressiveness. Culture effluent from tissue samples harvested from 19 individual patients who had undergone thyroidectomy for the treatment of suspected thyroid cancer was assessed, first using a proteome profiler™ angiogenesis array kit. Patients were subcategorised as ‘aggressive’ if they possessed a minimum of N1b level metastases, whilst ‘non‑aggressive’ samples were T3 or lower without evidence of multifocality; and contralateral healthy thyroid tissue was harvested for comparative studies. Levels of Serpin‑F1, vascular endothelial growth factor, Thrombospondin‑1 and chemokine (C‑C motif) ligand were significantly altered and, thus, were further investigated using ELISA to allow for quantitative analysis. The concentration of serpin‑F1 was significantly increased in the effluent of aggressive thyroid cancer tissue when compared with levels released by both non‑aggressive and benign samples. The present study demonstrated the usability of microfluidic technology for the analysis of the ex vivo tissue secretome in order to identify novel biomarkers.

Citation

Riley, A., Jones, H., England, J., Kuvshinov, D., Green, V., & Greenman, J. (2021). Identification of soluble tissue‑derived biomarkers from human thyroid tissue explants maintained on a microfluidic device. Oncology Letters, 22(5), https://doi.org/10.3892/ol.2021.13041

Journal Article Type Article
Acceptance Date Jun 3, 2021
Online Publication Date Sep 13, 2021
Publication Date 2021-11
Deposit Date Oct 6, 2021
Publicly Available Date Mar 14, 2022
Journal Oncology Letters
Print ISSN 1792-1074
Electronic ISSN 1792-1082
Publisher Spandidos Publications
Peer Reviewed Peer Reviewed
Volume 22
Issue 5
Article Number 780
DOI https://doi.org/10.3892/ol.2021.13041
Keywords Biomarker; Thyroid; Thyroid cancer; Microfluidics; Serpin F1
Public URL https://hull-repository.worktribe.com/output/3842353