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Propensity Score-Matched Analysis to Identify Pathways Associated with Loss of Sodium Iodide Symporter in Papillary Thyroid Cancer

Sodium iodide symporter (NIS) expression in thyroid follicular cells plays an important role in normal physiology and radioactive iodine therapy for thyroid cancer. Loss of NIS expression is often seen in thyroid cancers and may lead to radioiodine refractoriness. To explore novel mechanisms of NIS...

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Autores principales: Lee, Fang, Kuo, Chi-Yu, Tsai, Chung-Hsin, Cheng, Shih-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164071/
https://www.ncbi.nlm.nih.gov/pubmed/35723359
http://dx.doi.org/10.3390/cimb44040101
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author Lee, Fang
Kuo, Chi-Yu
Tsai, Chung-Hsin
Cheng, Shih-Ping
author_facet Lee, Fang
Kuo, Chi-Yu
Tsai, Chung-Hsin
Cheng, Shih-Ping
author_sort Lee, Fang
collection PubMed
description Sodium iodide symporter (NIS) expression in thyroid follicular cells plays an important role in normal physiology and radioactive iodine therapy for thyroid cancer. Loss of NIS expression is often seen in thyroid cancers and may lead to radioiodine refractoriness. To explore novel mechanisms of NIS repression beyond oncogenic drivers, clinical and RNA-seq data from the thyroid cancer dataset of The Cancer Genome Atlas were analyzed. Propensity score matching was used to control for various genetic background factors. We found that tumoral NIS expression was negatively correlated with tumor size. Additionally, low NIS expression was the only factor associated with recurrence-free survival in a Cox multivariate regression analysis. After matching for clinicopathologic profiles and driver mutations, the principal component analysis revealed distinct gene expressions between the high and low NIS groups. Gene set enrichment analysis suggested the downregulation of hedgehog signaling, immune networks, and cell adhesions. Positively enriched pathways included DNA replication, nucleotide excision repair, MYC, and Wnt/β-catenin pathways. In summary, we identified several potential targets which could be exploited to rescue the loss of NIS expression and develop redifferentiation strategies to facilitate radioactive iodine therapy for thyroid cancer.
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spelling pubmed-91640712022-06-04 Propensity Score-Matched Analysis to Identify Pathways Associated with Loss of Sodium Iodide Symporter in Papillary Thyroid Cancer Lee, Fang Kuo, Chi-Yu Tsai, Chung-Hsin Cheng, Shih-Ping Curr Issues Mol Biol Article Sodium iodide symporter (NIS) expression in thyroid follicular cells plays an important role in normal physiology and radioactive iodine therapy for thyroid cancer. Loss of NIS expression is often seen in thyroid cancers and may lead to radioiodine refractoriness. To explore novel mechanisms of NIS repression beyond oncogenic drivers, clinical and RNA-seq data from the thyroid cancer dataset of The Cancer Genome Atlas were analyzed. Propensity score matching was used to control for various genetic background factors. We found that tumoral NIS expression was negatively correlated with tumor size. Additionally, low NIS expression was the only factor associated with recurrence-free survival in a Cox multivariate regression analysis. After matching for clinicopathologic profiles and driver mutations, the principal component analysis revealed distinct gene expressions between the high and low NIS groups. Gene set enrichment analysis suggested the downregulation of hedgehog signaling, immune networks, and cell adhesions. Positively enriched pathways included DNA replication, nucleotide excision repair, MYC, and Wnt/β-catenin pathways. In summary, we identified several potential targets which could be exploited to rescue the loss of NIS expression and develop redifferentiation strategies to facilitate radioactive iodine therapy for thyroid cancer. MDPI 2022-03-26 /pmc/articles/PMC9164071/ /pubmed/35723359 http://dx.doi.org/10.3390/cimb44040101 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
Lee, Fang
Kuo, Chi-Yu
Tsai, Chung-Hsin
Cheng, Shih-Ping
Propensity Score-Matched Analysis to Identify Pathways Associated with Loss of Sodium Iodide Symporter in Papillary Thyroid Cancer
title Propensity Score-Matched Analysis to Identify Pathways Associated with Loss of Sodium Iodide Symporter in Papillary Thyroid Cancer
title_full Propensity Score-Matched Analysis to Identify Pathways Associated with Loss of Sodium Iodide Symporter in Papillary Thyroid Cancer
title_fullStr Propensity Score-Matched Analysis to Identify Pathways Associated with Loss of Sodium Iodide Symporter in Papillary Thyroid Cancer
title_full_unstemmed Propensity Score-Matched Analysis to Identify Pathways Associated with Loss of Sodium Iodide Symporter in Papillary Thyroid Cancer
title_short Propensity Score-Matched Analysis to Identify Pathways Associated with Loss of Sodium Iodide Symporter in Papillary Thyroid Cancer
title_sort propensity score-matched analysis to identify pathways associated with loss of sodium iodide symporter in papillary thyroid cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164071/
https://www.ncbi.nlm.nih.gov/pubmed/35723359
http://dx.doi.org/10.3390/cimb44040101
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