Oncotarget

Research Papers:

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

Cheng-Hsun Ho _, Huai-Chia Chuang, I-Chin Wu, Hung-Wen Tsai, Yih-Jyh Lin, Hung-Yu Sun, Kung-Chia Young, Yen-Cheng Chiu, Pin-Nan Cheng, Wen-Chun Liu, Tse-Hua Tan and Ting-Tsung Chang

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Oncotarget. 2016; 7:49765-49776. https://doi.org/10.18632/oncotarget.10176

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Abstract

Cheng-Hsun Ho1,2,*, Huai-Chia Chuang3,*, I-Chin Wu2, Hung-Wen Tsai4,5, Yih-Jyh Lin6, Hung-Yu Sun7, Kung-Chia Young7, Yen-Cheng Chiu2, Pin-Nan Cheng2, Wen-Chun Liu2,5, Tse-Hua Tan3,8, Ting-Tsung Chang2,5,9

1Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

2Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

3Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan

4Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

5Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan, Taiwan

6Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

7Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

8Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA

9Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Ting-Tsung Chang, email: ttchang@mail.ncku.edu.tw

Tse-Hua Tan, email: ttan@nhri.org.tw

Keywords: hepatocellular carcinoma, recurrence, GLK, NFκB

Received: September 08, 2015    Accepted: June 04, 2016    Published: June 20, 2016

ABSTRACT

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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