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The Prognostic Significance of Histone Demethylase UTX in Esophageal Squamous Cell Carcinoma

The dysregulation of the ubiquitously transcribed TPR gene on the X chromosome (UTX) has been reported to be involved in the oncogenesis of several types of cancers. However, the expression and significance of UTX in esophageal squamous cell carcinoma (ESCC) remains largely undetermined. Immunohisto...

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Autores principales: Li, Shau-Hsuan, Lu, Hung-I, Huang, Wan-Ting, Tien, Wan-Yu, Lan, Ya-Chun, Lin, Wei-Che, Tsai, Hsin-Ting, Chen, Chang-Han
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796242/
https://www.ncbi.nlm.nih.gov/pubmed/29351209
http://dx.doi.org/10.3390/ijms19010297
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author Li, Shau-Hsuan
Lu, Hung-I
Huang, Wan-Ting
Tien, Wan-Yu
Lan, Ya-Chun
Lin, Wei-Che
Tsai, Hsin-Ting
Chen, Chang-Han
author_facet Li, Shau-Hsuan
Lu, Hung-I
Huang, Wan-Ting
Tien, Wan-Yu
Lan, Ya-Chun
Lin, Wei-Che
Tsai, Hsin-Ting
Chen, Chang-Han
author_sort Li, Shau-Hsuan
collection PubMed
description The dysregulation of the ubiquitously transcribed TPR gene on the X chromosome (UTX) has been reported to be involved in the oncogenesis of several types of cancers. However, the expression and significance of UTX in esophageal squamous cell carcinoma (ESCC) remains largely undetermined. Immunohistochemistry was performed in 106 ESCC patients, and correlated with clinicopathological features and survival. The functional role of UTX in ESCC cells was determined by UTX-mediated siRNA. Univariate analyses showed that high UTX expression was associated with superior overall survival (OS, p = 0.011) and disease-free survival (DFS, p = 0.01). UTX overexpression was an independent prognosticator in multivariate analysis for OS (p = 0.013, hazard ratio = 1.996) and DFS (p = 0.009, hazard ratio = 1.972). The 5-year OS rates were 39% and 61% in patients with low expression and high expression of UTX, respectively. Inhibition of endogenous UTX in ESCC cells increased cell viability and BrdU incorporation, and decreased the expression of epithelial marker E-cadherin. Immunohistochemically, UTX expression was also positively correlated with E-cadherin expression. High UTX expression is independently associated with a better prognosis in patients with ESCC and downregulation of UTX increases ESCC cell growth and decreases E-cadherin expression. Our results suggest that UTX may be a novel therapeutic target for patients with ESCC.
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spelling pubmed-57962422018-02-09 The Prognostic Significance of Histone Demethylase UTX in Esophageal Squamous Cell Carcinoma Li, Shau-Hsuan Lu, Hung-I Huang, Wan-Ting Tien, Wan-Yu Lan, Ya-Chun Lin, Wei-Che Tsai, Hsin-Ting Chen, Chang-Han Int J Mol Sci Article The dysregulation of the ubiquitously transcribed TPR gene on the X chromosome (UTX) has been reported to be involved in the oncogenesis of several types of cancers. However, the expression and significance of UTX in esophageal squamous cell carcinoma (ESCC) remains largely undetermined. Immunohistochemistry was performed in 106 ESCC patients, and correlated with clinicopathological features and survival. The functional role of UTX in ESCC cells was determined by UTX-mediated siRNA. Univariate analyses showed that high UTX expression was associated with superior overall survival (OS, p = 0.011) and disease-free survival (DFS, p = 0.01). UTX overexpression was an independent prognosticator in multivariate analysis for OS (p = 0.013, hazard ratio = 1.996) and DFS (p = 0.009, hazard ratio = 1.972). The 5-year OS rates were 39% and 61% in patients with low expression and high expression of UTX, respectively. Inhibition of endogenous UTX in ESCC cells increased cell viability and BrdU incorporation, and decreased the expression of epithelial marker E-cadherin. Immunohistochemically, UTX expression was also positively correlated with E-cadherin expression. High UTX expression is independently associated with a better prognosis in patients with ESCC and downregulation of UTX increases ESCC cell growth and decreases E-cadherin expression. Our results suggest that UTX may be a novel therapeutic target for patients with ESCC. MDPI 2018-01-19 /pmc/articles/PMC5796242/ /pubmed/29351209 http://dx.doi.org/10.3390/ijms19010297 Text en © 2018 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Shau-Hsuan
Lu, Hung-I
Huang, Wan-Ting
Tien, Wan-Yu
Lan, Ya-Chun
Lin, Wei-Che
Tsai, Hsin-Ting
Chen, Chang-Han
The Prognostic Significance of Histone Demethylase UTX in Esophageal Squamous Cell Carcinoma
title The Prognostic Significance of Histone Demethylase UTX in Esophageal Squamous Cell Carcinoma
title_full The Prognostic Significance of Histone Demethylase UTX in Esophageal Squamous Cell Carcinoma
title_fullStr The Prognostic Significance of Histone Demethylase UTX in Esophageal Squamous Cell Carcinoma
title_full_unstemmed The Prognostic Significance of Histone Demethylase UTX in Esophageal Squamous Cell Carcinoma
title_short The Prognostic Significance of Histone Demethylase UTX in Esophageal Squamous Cell Carcinoma
title_sort prognostic significance of histone demethylase utx in esophageal squamous cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796242/
https://www.ncbi.nlm.nih.gov/pubmed/29351209
http://dx.doi.org/10.3390/ijms19010297
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