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Eukaryotic elongation factor-2 kinase expression is an independent prognostic factor in colorectal cancer

BACKGROUND: Prognostication of patients with colorectal cancer (CRC) currently relies on tumor-node-metastasis (TNM) staging but clinical outcomes of patients of the same histoclinical stage are heterogeneous. It is therefore imperative to devise novel molecular tests to stratify CRC patients. Our p...

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Autores principales: Ng, Tung H., Sham, Kathy W. Y., Xie, Chuan M., Ng, Simon S. M., To, Ka F., Tong, Joanna H. M., Liu, Wing Y. Z., Zhang, Lin, Chan, Matthew T. V., Wu, William K. K., Cheng, Christopher H. K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607603/
https://www.ncbi.nlm.nih.gov/pubmed/31266475
http://dx.doi.org/10.1186/s12885-019-5873-0
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author Ng, Tung H.
Sham, Kathy W. Y.
Xie, Chuan M.
Ng, Simon S. M.
To, Ka F.
Tong, Joanna H. M.
Liu, Wing Y. Z.
Zhang, Lin
Chan, Matthew T. V.
Wu, William K. K.
Cheng, Christopher H. K.
author_facet Ng, Tung H.
Sham, Kathy W. Y.
Xie, Chuan M.
Ng, Simon S. M.
To, Ka F.
Tong, Joanna H. M.
Liu, Wing Y. Z.
Zhang, Lin
Chan, Matthew T. V.
Wu, William K. K.
Cheng, Christopher H. K.
author_sort Ng, Tung H.
collection PubMed
description BACKGROUND: Prognostication of patients with colorectal cancer (CRC) currently relies on tumor-node-metastasis (TNM) staging but clinical outcomes of patients of the same histoclinical stage are heterogeneous. It is therefore imperative to devise novel molecular tests to stratify CRC patients. Our previous work demonstrated that eukaryotic elongation factor-2 kinase (EEF2K) is a tumor suppressor in CRC. Herein, we investigated EEF2K expression in CRC and determined its relationship with clinicopathological parameters. METHODS: Quantitative RT-PCR and Westerns blots were used to examine EEF2K expression in primary tumor and the adjacent non-tumor tissues of CRC patients (n = 20). Kaplan-Meier curves and Cox regression analysis were used to assess the association between clinical outcomes of CRC patients and EEF2K protein expression determined by immunohistochemistry on tissue microarray (n = 151). RESULTS: EEF2K was significantly downregulated at both mRNA and protein levels in tumors of CRC patients. Univariate Cox regression analysis revealed that CRC patients with high tumor grade, advanced TNM staging and low EEF2K expression were associated with worse overall survival. Multivariate analysis further demonstrated that low EEF2K expression was an independent factor for predicting poorer overall survival in CRC patients (p = 0.014; Hazard ratio = 2.951; 95% confidence interval: 1.240–7.024). The 5-year survival rate was 82.8% in the EEF2K-high-expression group versus 63.9% in the EEF2K-low-expression group (p = 0.0118). The association of overall survival with EEF2K expression in CRC patients was verified in The Cancer Genome Atlas (TCGA) cohort. CONCLUSIONS: EEF2K is downregulated in CRC and its expression can be employed as a prognostic marker for CRC patients independent of TNM staging. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-5873-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-66076032019-07-12 Eukaryotic elongation factor-2 kinase expression is an independent prognostic factor in colorectal cancer Ng, Tung H. Sham, Kathy W. Y. Xie, Chuan M. Ng, Simon S. M. To, Ka F. Tong, Joanna H. M. Liu, Wing Y. Z. Zhang, Lin Chan, Matthew T. V. Wu, William K. K. Cheng, Christopher H. K. BMC Cancer Research Article BACKGROUND: Prognostication of patients with colorectal cancer (CRC) currently relies on tumor-node-metastasis (TNM) staging but clinical outcomes of patients of the same histoclinical stage are heterogeneous. It is therefore imperative to devise novel molecular tests to stratify CRC patients. Our previous work demonstrated that eukaryotic elongation factor-2 kinase (EEF2K) is a tumor suppressor in CRC. Herein, we investigated EEF2K expression in CRC and determined its relationship with clinicopathological parameters. METHODS: Quantitative RT-PCR and Westerns blots were used to examine EEF2K expression in primary tumor and the adjacent non-tumor tissues of CRC patients (n = 20). Kaplan-Meier curves and Cox regression analysis were used to assess the association between clinical outcomes of CRC patients and EEF2K protein expression determined by immunohistochemistry on tissue microarray (n = 151). RESULTS: EEF2K was significantly downregulated at both mRNA and protein levels in tumors of CRC patients. Univariate Cox regression analysis revealed that CRC patients with high tumor grade, advanced TNM staging and low EEF2K expression were associated with worse overall survival. Multivariate analysis further demonstrated that low EEF2K expression was an independent factor for predicting poorer overall survival in CRC patients (p = 0.014; Hazard ratio = 2.951; 95% confidence interval: 1.240–7.024). The 5-year survival rate was 82.8% in the EEF2K-high-expression group versus 63.9% in the EEF2K-low-expression group (p = 0.0118). The association of overall survival with EEF2K expression in CRC patients was verified in The Cancer Genome Atlas (TCGA) cohort. CONCLUSIONS: EEF2K is downregulated in CRC and its expression can be employed as a prognostic marker for CRC patients independent of TNM staging. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-5873-0) contains supplementary material, which is available to authorized users. BioMed Central 2019-07-02 /pmc/articles/PMC6607603/ /pubmed/31266475 http://dx.doi.org/10.1186/s12885-019-5873-0 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Ng, Tung H.
Sham, Kathy W. Y.
Xie, Chuan M.
Ng, Simon S. M.
To, Ka F.
Tong, Joanna H. M.
Liu, Wing Y. Z.
Zhang, Lin
Chan, Matthew T. V.
Wu, William K. K.
Cheng, Christopher H. K.
Eukaryotic elongation factor-2 kinase expression is an independent prognostic factor in colorectal cancer
title Eukaryotic elongation factor-2 kinase expression is an independent prognostic factor in colorectal cancer
title_full Eukaryotic elongation factor-2 kinase expression is an independent prognostic factor in colorectal cancer
title_fullStr Eukaryotic elongation factor-2 kinase expression is an independent prognostic factor in colorectal cancer
title_full_unstemmed Eukaryotic elongation factor-2 kinase expression is an independent prognostic factor in colorectal cancer
title_short Eukaryotic elongation factor-2 kinase expression is an independent prognostic factor in colorectal cancer
title_sort eukaryotic elongation factor-2 kinase expression is an independent prognostic factor in colorectal cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607603/
https://www.ncbi.nlm.nih.gov/pubmed/31266475
http://dx.doi.org/10.1186/s12885-019-5873-0
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