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Identification of an immune-related signature indicating the dedifferentiation of thyroid cells

BACKGROUND: Immune cells account for a large proportion of the tumour microenvironment in anaplastic thyroid carcinomas (ATCs). However, the expression pattern of immune-related genes (IRGs) in ATCs is unclear. Our study aimed to identify an immune-related signature indicating the dedifferentiation...

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Autores principales: Wang, Xuemin, Peng, Wen, Li, Chunyan, Qin, Rujia, Zhong, Zhaoming, Sun, Chuanzheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067302/
https://www.ncbi.nlm.nih.gov/pubmed/33892730
http://dx.doi.org/10.1186/s12935-021-01939-3
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author Wang, Xuemin
Peng, Wen
Li, Chunyan
Qin, Rujia
Zhong, Zhaoming
Sun, Chuanzheng
author_facet Wang, Xuemin
Peng, Wen
Li, Chunyan
Qin, Rujia
Zhong, Zhaoming
Sun, Chuanzheng
author_sort Wang, Xuemin
collection PubMed
description BACKGROUND: Immune cells account for a large proportion of the tumour microenvironment in anaplastic thyroid carcinomas (ATCs). However, the expression pattern of immune-related genes (IRGs) in ATCs is unclear. Our study aimed to identify an immune-related signature indicating the dedifferentiation of thyroid cells. METHODS: We compared the differences in thyroid differentiation score (TDS), infiltration of immune cells and enriched pathways between ATCs and papillary thyroid carcinomas (PTCs) or normal thyroid tissues in the Gene Expression Omnibus database. Univariate and multivariable Cox analyses were used to screen prognosis-associated IRGs in The Cancer Genome Atlas database. After constructing a risk score, we investigated its predictive value for differentiation and survival by applying receiver operating characteristic and Kaplan–Meier curves. We further explored its associations with important immune checkpoint molecules, infiltrating immune cells and response to immunotherapy. RESULTS: Compared with PTCs or normal thyroid tissues, ATCs exhibited lower TDS values and higher enrichment of immune cells and activation of the inflammatory response. The quantitative analyses and immunohistochemical staining validated that most ATC cell lines and ATC tissues had higher expression of MMP9 and lower expression of SDC2 than normal thyroid samples and PTC. Higher risk scores indicates dedifferentiation and a worse prognosis. Additionally, the risk score was positively correlated with the immune checkpoint molecules PDL1, CTLA4, IDO1, and HAVCR2 and infiltration of multiple immune cells. Importantly, we found that the samples with higher risk scores tended to have a better response to immunotherapy than those with lower scores. CONCLUSION: Our findings indicate that the risk score may not only contribute to the determination of differentiation and prognosis of thyroid carcinomas but also help the prediction of immune cells infiltration and immunotherapy response. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-01939-3.
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spelling pubmed-80673022021-04-26 Identification of an immune-related signature indicating the dedifferentiation of thyroid cells Wang, Xuemin Peng, Wen Li, Chunyan Qin, Rujia Zhong, Zhaoming Sun, Chuanzheng Cancer Cell Int Primary Research BACKGROUND: Immune cells account for a large proportion of the tumour microenvironment in anaplastic thyroid carcinomas (ATCs). However, the expression pattern of immune-related genes (IRGs) in ATCs is unclear. Our study aimed to identify an immune-related signature indicating the dedifferentiation of thyroid cells. METHODS: We compared the differences in thyroid differentiation score (TDS), infiltration of immune cells and enriched pathways between ATCs and papillary thyroid carcinomas (PTCs) or normal thyroid tissues in the Gene Expression Omnibus database. Univariate and multivariable Cox analyses were used to screen prognosis-associated IRGs in The Cancer Genome Atlas database. After constructing a risk score, we investigated its predictive value for differentiation and survival by applying receiver operating characteristic and Kaplan–Meier curves. We further explored its associations with important immune checkpoint molecules, infiltrating immune cells and response to immunotherapy. RESULTS: Compared with PTCs or normal thyroid tissues, ATCs exhibited lower TDS values and higher enrichment of immune cells and activation of the inflammatory response. The quantitative analyses and immunohistochemical staining validated that most ATC cell lines and ATC tissues had higher expression of MMP9 and lower expression of SDC2 than normal thyroid samples and PTC. Higher risk scores indicates dedifferentiation and a worse prognosis. Additionally, the risk score was positively correlated with the immune checkpoint molecules PDL1, CTLA4, IDO1, and HAVCR2 and infiltration of multiple immune cells. Importantly, we found that the samples with higher risk scores tended to have a better response to immunotherapy than those with lower scores. CONCLUSION: Our findings indicate that the risk score may not only contribute to the determination of differentiation and prognosis of thyroid carcinomas but also help the prediction of immune cells infiltration and immunotherapy response. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-01939-3. BioMed Central 2021-04-23 /pmc/articles/PMC8067302/ /pubmed/33892730 http://dx.doi.org/10.1186/s12935-021-01939-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Wang, Xuemin
Peng, Wen
Li, Chunyan
Qin, Rujia
Zhong, Zhaoming
Sun, Chuanzheng
Identification of an immune-related signature indicating the dedifferentiation of thyroid cells
title Identification of an immune-related signature indicating the dedifferentiation of thyroid cells
title_full Identification of an immune-related signature indicating the dedifferentiation of thyroid cells
title_fullStr Identification of an immune-related signature indicating the dedifferentiation of thyroid cells
title_full_unstemmed Identification of an immune-related signature indicating the dedifferentiation of thyroid cells
title_short Identification of an immune-related signature indicating the dedifferentiation of thyroid cells
title_sort identification of an immune-related signature indicating the dedifferentiation of thyroid cells
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067302/
https://www.ncbi.nlm.nih.gov/pubmed/33892730
http://dx.doi.org/10.1186/s12935-021-01939-3
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