Epithelial-to-mesenchymal transition and its association with PD-L1 and CD8 in thyroid cancer

Epithelial-to-mesenchymal transition and its association with PD-L1 and CD8 in thyroid cancer.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1530/EC-20-0268
Journal or Publication Title: Endocrine Connections
Volume: 9
Number: 10
Page Range: pp. 1028-1041
Date: October 2020
Divisions: Computational BioMedicine
Depositing User: General Admin
Identification Number: 10.1530/EC-20-0268
ISSN: 2049-3614
Date Deposited: 10 Oct 2021 10:31

Programmed cell death-ligand 1 (PD-L1) has recently been shown to play a role in the regulation of epithelial-to-mesenchymal transition (EMT); however, the relationship between PD-L1 expression, EMT and the inflammatory tumour microenvironment has yet to be investigated in thyroid cancer. To address this issue, we examined the expression of CD8, PD-L1 and the EMT markers E-cadherin and vimentin in a cohort of 74 papillary thyroid cancer (PTC) patients and investigated the association of these with clinicopathologic characteristics and disease-free survival (DFS). The relationship between PD-L1 and EMT was further examined in three thyroid cancer cell lines via Western blot and live cell imaging. In order to expand our in vitro findings, the normalised gene expression profiles of 516 thyroid cancer patients were retrieved and analysed from The Cancer Genome Atlas (TCGA). PD-L1 positivity was significantly higher in PTC patients exhibiting a mesenchymal phenotype (P = 0.012). Kaplan-Meier analysis revealed that PD-L1 (P = 0.045), CD8 (P = 0.038) and EMT status (P = 0.038) were all significant predictors for DFS. Sub-analysis confirmed that the poorest DFS was evident in PD-L1 positive patients with EMT features and negative CD8 expression (P < 0.0001). IFN-γ treatment induced upregulation of PD-L1 and significantly promoted an EMT phenotype in two thyroid cancer cell lines. Our findings suggest that PD-L1 signalling may play a role in stimulating EMT in thyroid cancer. EMT, CD8 and PD-L1 expression may serve as valuable predictive biomarkers in patients with PTC.

Keywords: CD8; epithelial-to-mesenchymal transition; programmed cell death-ligand 1; survival; thyroid cancer.

Aghajani, Marra Jai
Yang, Tao
Schmitz, Ulf
James, Alexander
McCafferty, Charles Eugenio
de Souza, Paul
Niles, Navin
Roberts, Tara L
Last Modified: 10 Oct 2021 10:31
URI: https://eprints.centenary.org.au/id/eprint/1138

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