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Comprehensive Analysis of the Prognosis and Drug Sensitivity of Differentiation-Related lncRNAs in Papillary Thyroid Cancer
SIMPLE SUMMARY: Merging evidence has indicated that dedifferentiation is the main concern associated with radioactive iodine (RAI) refractoriness in patients with papillary thyroid cancer (PTC), and the underlying mechanisms of PTC dedifferentiation remain unclear. This study systematically delineat...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909347/ https://www.ncbi.nlm.nih.gov/pubmed/35267662 http://dx.doi.org/10.3390/cancers14051353 |
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author | Wang, Wenlong Bai, Ning Li, Xinying |
author_facet | Wang, Wenlong Bai, Ning Li, Xinying |
author_sort | Wang, Wenlong |
collection | PubMed |
description | SIMPLE SUMMARY: Merging evidence has indicated that dedifferentiation is the main concern associated with radioactive iodine (RAI) refractoriness in patients with papillary thyroid cancer (PTC), and the underlying mechanisms of PTC dedifferentiation remain unclear. This study systematically delineated the expression pattern, tumor immune microenvironment, drug sensitivity, and prognostic value of differentiation-related lncRNAs. It also demonstrated that DPH6-DT could be considered as a novel signature to indicate differentiation and promote TC progression via activating the PI3K-AKT signaling pathway. ABSTRACT: Dedifferentiation is the main concern associated with radioactive iodine (RAI) refractoriness in patients with papillary thyroid cancer (PTC), and the underlying mechanisms of PTC dedifferentiation remain unclear. The present work aimed to identify a useful signature to indicate dedifferentiation and further explore its role in prognosis and susceptibility to chemotherapy drugs. A total of five prognostic-related DR-lncRNAs were selected to establish a prognostic-predicting model, and corresponding risk scores were closely associated with the infiltration of immune cells and immune checkpoint blockade. Moreover, we built an integrated nomogram based on DR-lncRNAs and age that showed a strong ability to predict the 3- and 5-year overall survival. Interestingly, drug sensitivity analysis revealed that the low-risk group was more sensitive to Bendamustine and TAS-6417 than the high-risk group. In addition, knockdown of DR-lncRNAs (DPH6-DT) strongly promoted cell proliferation, invasion, and migration via PI3K-AKT signal pathway in vitro. Furthermore, DPH6-DT downregulation also increased the expression of vimentin and N-cadherin during epithelial-mesenchymal transition. This study firstly confirms that DR-lncRNAs play a vital role in the prognosis and immune cells infiltration in patients with PTC, as well as a predictor of the drugs’ chemosensitivity. Based on our results, DR-lncRNAs can serve as a promising prognostic biomarkers and treatment targets. |
format | Online Article Text |
id | pubmed-8909347 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89093472022-03-11 Comprehensive Analysis of the Prognosis and Drug Sensitivity of Differentiation-Related lncRNAs in Papillary Thyroid Cancer Wang, Wenlong Bai, Ning Li, Xinying Cancers (Basel) Article SIMPLE SUMMARY: Merging evidence has indicated that dedifferentiation is the main concern associated with radioactive iodine (RAI) refractoriness in patients with papillary thyroid cancer (PTC), and the underlying mechanisms of PTC dedifferentiation remain unclear. This study systematically delineated the expression pattern, tumor immune microenvironment, drug sensitivity, and prognostic value of differentiation-related lncRNAs. It also demonstrated that DPH6-DT could be considered as a novel signature to indicate differentiation and promote TC progression via activating the PI3K-AKT signaling pathway. ABSTRACT: Dedifferentiation is the main concern associated with radioactive iodine (RAI) refractoriness in patients with papillary thyroid cancer (PTC), and the underlying mechanisms of PTC dedifferentiation remain unclear. The present work aimed to identify a useful signature to indicate dedifferentiation and further explore its role in prognosis and susceptibility to chemotherapy drugs. A total of five prognostic-related DR-lncRNAs were selected to establish a prognostic-predicting model, and corresponding risk scores were closely associated with the infiltration of immune cells and immune checkpoint blockade. Moreover, we built an integrated nomogram based on DR-lncRNAs and age that showed a strong ability to predict the 3- and 5-year overall survival. Interestingly, drug sensitivity analysis revealed that the low-risk group was more sensitive to Bendamustine and TAS-6417 than the high-risk group. In addition, knockdown of DR-lncRNAs (DPH6-DT) strongly promoted cell proliferation, invasion, and migration via PI3K-AKT signal pathway in vitro. Furthermore, DPH6-DT downregulation also increased the expression of vimentin and N-cadherin during epithelial-mesenchymal transition. This study firstly confirms that DR-lncRNAs play a vital role in the prognosis and immune cells infiltration in patients with PTC, as well as a predictor of the drugs’ chemosensitivity. Based on our results, DR-lncRNAs can serve as a promising prognostic biomarkers and treatment targets. MDPI 2022-03-07 /pmc/articles/PMC8909347/ /pubmed/35267662 http://dx.doi.org/10.3390/cancers14051353 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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/). |
spellingShingle | Article Wang, Wenlong Bai, Ning Li, Xinying Comprehensive Analysis of the Prognosis and Drug Sensitivity of Differentiation-Related lncRNAs in Papillary Thyroid Cancer |
title | Comprehensive Analysis of the Prognosis and Drug Sensitivity of Differentiation-Related lncRNAs in Papillary Thyroid Cancer |
title_full | Comprehensive Analysis of the Prognosis and Drug Sensitivity of Differentiation-Related lncRNAs in Papillary Thyroid Cancer |
title_fullStr | Comprehensive Analysis of the Prognosis and Drug Sensitivity of Differentiation-Related lncRNAs in Papillary Thyroid Cancer |
title_full_unstemmed | Comprehensive Analysis of the Prognosis and Drug Sensitivity of Differentiation-Related lncRNAs in Papillary Thyroid Cancer |
title_short | Comprehensive Analysis of the Prognosis and Drug Sensitivity of Differentiation-Related lncRNAs in Papillary Thyroid Cancer |
title_sort | comprehensive analysis of the prognosis and drug sensitivity of differentiation-related lncrnas in papillary thyroid cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909347/ https://www.ncbi.nlm.nih.gov/pubmed/35267662 http://dx.doi.org/10.3390/cancers14051353 |
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