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Prediction of early hepatocellular carcinoma recurrence using germinal center kinase-like kinase

Germinal center kinase-like kinase (GLK) is a key controller of autoimmunity. In this study, we assessed the clinical relevance and tumorigenic effects of GLK in hepatocellular carcinoma (HCC). Using immunohistochemistry, we showed that the GLK proportion score increased in both cancerous and adjace...

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Autores principales: Ho, Cheng-Hsun, Chuang, Huai-Chia, Wu, I-Chin, Tsai, Hung-Wen, Lin, Yih-Jyh, Sun, Hung-Yu, Young, Kung-Chia, Chiu, Yen-Cheng, Cheng, Pin-Nan, Liu, Wen-Chun, Tan, Tse-Hua, Chang, Ting-Tsung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226546/
https://www.ncbi.nlm.nih.gov/pubmed/27343552
http://dx.doi.org/10.18632/oncotarget.10176
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author Ho, Cheng-Hsun
Chuang, Huai-Chia
Wu, I-Chin
Tsai, Hung-Wen
Lin, Yih-Jyh
Sun, Hung-Yu
Young, Kung-Chia
Chiu, Yen-Cheng
Cheng, Pin-Nan
Liu, Wen-Chun
Tan, Tse-Hua
Chang, Ting-Tsung
author_facet Ho, Cheng-Hsun
Chuang, Huai-Chia
Wu, I-Chin
Tsai, Hung-Wen
Lin, Yih-Jyh
Sun, Hung-Yu
Young, Kung-Chia
Chiu, Yen-Cheng
Cheng, Pin-Nan
Liu, Wen-Chun
Tan, Tse-Hua
Chang, Ting-Tsung
author_sort Ho, Cheng-Hsun
collection PubMed
description Germinal center kinase-like kinase (GLK) is a key controller of autoimmunity. In this study, we assessed the clinical relevance and tumorigenic effects of GLK in hepatocellular carcinoma (HCC). Using immunohistochemistry, we showed that the GLK proportion score increased in both cancerous and adjacent non-cancerous liver tissue from patients with HCC recurrence. A Kaplan-Meier analysis revealed that patients with a wide distribution of GLK in non-cancerous liver tissue had a higher rate of HCC recurrence than those with very low or no GLK expression. Multivariate Cox regression analyses indicated that a high GLK proportion score in non-cancerous liver tissue was an independent predictor of early HCC recurrence after resection. Lentiviral vector-mediated overexpression of GLK activated the nuclear factor kappa B (NFκB) signaling cascade and accelerated cell cycle progression in primary human hepatocytes, thereby promoting proliferation. An increase in GLK expression coincided with NFκB activation and enhanced expression of proliferating cell nuclear antigen in HCC tissue. Our findings demonstrate a potential hepatocarcinogenic effect of GLK and the feasibility of using GLK to predict early HCC recurrence.
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spelling pubmed-52265462017-01-18 Prediction of early hepatocellular carcinoma recurrence using germinal center kinase-like kinase Ho, Cheng-Hsun Chuang, Huai-Chia Wu, I-Chin Tsai, Hung-Wen Lin, Yih-Jyh Sun, Hung-Yu Young, Kung-Chia Chiu, Yen-Cheng Cheng, Pin-Nan Liu, Wen-Chun Tan, Tse-Hua Chang, Ting-Tsung Oncotarget Research Paper Germinal center kinase-like kinase (GLK) is a key controller of autoimmunity. In this study, we assessed the clinical relevance and tumorigenic effects of GLK in hepatocellular carcinoma (HCC). Using immunohistochemistry, we showed that the GLK proportion score increased in both cancerous and adjacent non-cancerous liver tissue from patients with HCC recurrence. A Kaplan-Meier analysis revealed that patients with a wide distribution of GLK in non-cancerous liver tissue had a higher rate of HCC recurrence than those with very low or no GLK expression. Multivariate Cox regression analyses indicated that a high GLK proportion score in non-cancerous liver tissue was an independent predictor of early HCC recurrence after resection. Lentiviral vector-mediated overexpression of GLK activated the nuclear factor kappa B (NFκB) signaling cascade and accelerated cell cycle progression in primary human hepatocytes, thereby promoting proliferation. An increase in GLK expression coincided with NFκB activation and enhanced expression of proliferating cell nuclear antigen in HCC tissue. Our findings demonstrate a potential hepatocarcinogenic effect of GLK and the feasibility of using GLK to predict early HCC recurrence. Impact Journals LLC 2016-06-20 /pmc/articles/PMC5226546/ /pubmed/27343552 http://dx.doi.org/10.18632/oncotarget.10176 Text en Copyright: © 2016 Ho et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Ho, Cheng-Hsun
Chuang, Huai-Chia
Wu, I-Chin
Tsai, Hung-Wen
Lin, Yih-Jyh
Sun, Hung-Yu
Young, Kung-Chia
Chiu, Yen-Cheng
Cheng, Pin-Nan
Liu, Wen-Chun
Tan, Tse-Hua
Chang, Ting-Tsung
Prediction of early hepatocellular carcinoma recurrence using germinal center kinase-like kinase
title Prediction of early hepatocellular carcinoma recurrence using germinal center kinase-like kinase
title_full Prediction of early hepatocellular carcinoma recurrence using germinal center kinase-like kinase
title_fullStr Prediction of early hepatocellular carcinoma recurrence using germinal center kinase-like kinase
title_full_unstemmed Prediction of early hepatocellular carcinoma recurrence using germinal center kinase-like kinase
title_short Prediction of early hepatocellular carcinoma recurrence using germinal center kinase-like kinase
title_sort prediction of early hepatocellular carcinoma recurrence using germinal center kinase-like kinase
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226546/
https://www.ncbi.nlm.nih.gov/pubmed/27343552
http://dx.doi.org/10.18632/oncotarget.10176
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