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

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...

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Autores principales: Aghajani, Marra Jai, Yang, Tao, Schmitz, Ulf, James, Alexander, McCafferty, Charles Eugenio, de Souza, Paul, Niles, Navin, Roberts, Tara L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707834/
https://www.ncbi.nlm.nih.gov/pubmed/33112841
http://dx.doi.org/10.1530/EC-20-0268
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author Aghajani, Marra Jai
Yang, Tao
Schmitz, Ulf
James, Alexander
McCafferty, Charles Eugenio
de Souza, Paul
Niles, Navin
Roberts, Tara L
author_facet Aghajani, Marra Jai
Yang, Tao
Schmitz, Ulf
James, Alexander
McCafferty, Charles Eugenio
de Souza, Paul
Niles, Navin
Roberts, Tara L
author_sort Aghajani, Marra Jai
collection PubMed
description 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.
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spelling pubmed-77078342020-12-07 Epithelial-to-mesenchymal transition and its association with PD-L1 and CD8 in thyroid cancer Aghajani, Marra Jai Yang, Tao Schmitz, Ulf James, Alexander McCafferty, Charles Eugenio de Souza, Paul Niles, Navin Roberts, Tara L Endocr Connect Research 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. Bioscientifica Ltd 2020-09-28 /pmc/articles/PMC7707834/ /pubmed/33112841 http://dx.doi.org/10.1530/EC-20-0268 Text en © 2020 The authors http://creativecommons.org/licenses/by-nc/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Research
Aghajani, Marra Jai
Yang, Tao
Schmitz, Ulf
James, Alexander
McCafferty, Charles Eugenio
de Souza, Paul
Niles, Navin
Roberts, Tara L
Epithelial-to-mesenchymal transition and its association with PD-L1 and CD8 in thyroid cancer
title Epithelial-to-mesenchymal transition and its association with PD-L1 and CD8 in thyroid cancer
title_full Epithelial-to-mesenchymal transition and its association with PD-L1 and CD8 in thyroid cancer
title_fullStr Epithelial-to-mesenchymal transition and its association with PD-L1 and CD8 in thyroid cancer
title_full_unstemmed Epithelial-to-mesenchymal transition and its association with PD-L1 and CD8 in thyroid cancer
title_short Epithelial-to-mesenchymal transition and its association with PD-L1 and CD8 in thyroid cancer
title_sort epithelial-to-mesenchymal transition and its association with pd-l1 and cd8 in thyroid cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707834/
https://www.ncbi.nlm.nih.gov/pubmed/33112841
http://dx.doi.org/10.1530/EC-20-0268
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