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Prediction of novel target genes and pathways involved in tall cell variant papillary thyroid carcinoma

BACKGROUND: Tall cell variant papillary thyroid carcinoma (TCPTC) is reportedly associated with aggressive clinicopathological parameters and poor outcomes; however, the molecular mechanisms underlying TCPTC remain poorly understood. METHODS: The gene mutation types and mRNA expression profiles of p...

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Autores principales: Xia, Fada, Jiang, Bo, Chen, Yong, Du, Xin, Peng, Yao, Wang, Wenlong, Wang, Zhuolu, Li, Xinying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319788/
https://www.ncbi.nlm.nih.gov/pubmed/30572540
http://dx.doi.org/10.1097/MD.0000000000013802
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author Xia, Fada
Jiang, Bo
Chen, Yong
Du, Xin
Peng, Yao
Wang, Wenlong
Wang, Zhuolu
Li, Xinying
author_facet Xia, Fada
Jiang, Bo
Chen, Yong
Du, Xin
Peng, Yao
Wang, Wenlong
Wang, Zhuolu
Li, Xinying
author_sort Xia, Fada
collection PubMed
description BACKGROUND: Tall cell variant papillary thyroid carcinoma (TCPTC) is reportedly associated with aggressive clinicopathological parameters and poor outcomes; however, the molecular mechanisms underlying TCPTC remain poorly understood. METHODS: The gene mutation types and mRNA expression profiles of patients with TCPTC were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were identified. Pathways in the interaction network and the diagnostic approaches of candidate markers for TCPTC were investigated. RESULTS: BRAF mutation was particularly prevalent in TCPTC with a mutation frequency of 78%. TCPTC was associated with a patient age >45 years, tumor multifocality, extrathyroidal extension, a higher T stage, advanced AJCC TNM stages, BRAF V600E mutation, and poor disease-free survival. We identified 4138 TCPTC-related DEGs and 301 TCPTC-specific DEGs. Intriguingly, the gene expression pattern revealed that the dysregulated levels of both putative oncogenes and tumor suppressors in TCPTC were higher than those in classical/conventional variant PTC (cPTC). Functional enrichment analyses revealed that these DEGs were involved in several cancer-related pathways. A protein-protein interaction (PPI) network was constructed from the 301 TCPTC-specific DEGs, and 3 subnetworks, and 8 hub genes were verified. Receiver operating characteristic (ROC) analyses revealed that 6 hub genes, including COL5A1, COL1A1, COL10A1, COL11A1, CCL20, and CXCL5, could be used not only for the differential diagnosis of PTC from normal samples, but also for the differential diagnosis of TCPTC from cPTC samples. CONCLUSIONS: Our study might provide further insights into the investigations of the tumorigenesis mechanism of TCPTC and assists in the discovery of novel candidate diagnostic markers for TCPTC.
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spelling pubmed-63197882019-01-24 Prediction of novel target genes and pathways involved in tall cell variant papillary thyroid carcinoma Xia, Fada Jiang, Bo Chen, Yong Du, Xin Peng, Yao Wang, Wenlong Wang, Zhuolu Li, Xinying Medicine (Baltimore) Research Article BACKGROUND: Tall cell variant papillary thyroid carcinoma (TCPTC) is reportedly associated with aggressive clinicopathological parameters and poor outcomes; however, the molecular mechanisms underlying TCPTC remain poorly understood. METHODS: The gene mutation types and mRNA expression profiles of patients with TCPTC were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were identified. Pathways in the interaction network and the diagnostic approaches of candidate markers for TCPTC were investigated. RESULTS: BRAF mutation was particularly prevalent in TCPTC with a mutation frequency of 78%. TCPTC was associated with a patient age >45 years, tumor multifocality, extrathyroidal extension, a higher T stage, advanced AJCC TNM stages, BRAF V600E mutation, and poor disease-free survival. We identified 4138 TCPTC-related DEGs and 301 TCPTC-specific DEGs. Intriguingly, the gene expression pattern revealed that the dysregulated levels of both putative oncogenes and tumor suppressors in TCPTC were higher than those in classical/conventional variant PTC (cPTC). Functional enrichment analyses revealed that these DEGs were involved in several cancer-related pathways. A protein-protein interaction (PPI) network was constructed from the 301 TCPTC-specific DEGs, and 3 subnetworks, and 8 hub genes were verified. Receiver operating characteristic (ROC) analyses revealed that 6 hub genes, including COL5A1, COL1A1, COL10A1, COL11A1, CCL20, and CXCL5, could be used not only for the differential diagnosis of PTC from normal samples, but also for the differential diagnosis of TCPTC from cPTC samples. CONCLUSIONS: Our study might provide further insights into the investigations of the tumorigenesis mechanism of TCPTC and assists in the discovery of novel candidate diagnostic markers for TCPTC. Wolters Kluwer Health 2018-12-21 /pmc/articles/PMC6319788/ /pubmed/30572540 http://dx.doi.org/10.1097/MD.0000000000013802 Text en Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc. http://creativecommons.org/licenses/by/4.0 This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0
spellingShingle Research Article
Xia, Fada
Jiang, Bo
Chen, Yong
Du, Xin
Peng, Yao
Wang, Wenlong
Wang, Zhuolu
Li, Xinying
Prediction of novel target genes and pathways involved in tall cell variant papillary thyroid carcinoma
title Prediction of novel target genes and pathways involved in tall cell variant papillary thyroid carcinoma
title_full Prediction of novel target genes and pathways involved in tall cell variant papillary thyroid carcinoma
title_fullStr Prediction of novel target genes and pathways involved in tall cell variant papillary thyroid carcinoma
title_full_unstemmed Prediction of novel target genes and pathways involved in tall cell variant papillary thyroid carcinoma
title_short Prediction of novel target genes and pathways involved in tall cell variant papillary thyroid carcinoma
title_sort prediction of novel target genes and pathways involved in tall cell variant papillary thyroid carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319788/
https://www.ncbi.nlm.nih.gov/pubmed/30572540
http://dx.doi.org/10.1097/MD.0000000000013802
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