title: Prediction of early hepatocellular carcinoma recurrence using germinal center kinase-like kinase.
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.
authors.affiliation: Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Cheng-Hsun
authors.initials: CH
authors.lastname: Ho
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Huai-Chia
authors.initials: HC
authors.lastname: Chuang
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: I-Chin
authors.initials: IC
authors.lastname: Wu
authors.affiliation: Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Hung-Wen
authors.initials: HW
authors.lastname: Tsai
authors.affiliation: Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yih-Jyh
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Hung-Yu
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Kung-Chia
authors.initials: KC
authors.lastname: Young
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yen-Cheng
authors.initials: YC
authors.lastname: Chiu
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Pin-Nan
authors.initials: PN
authors.lastname: Cheng
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Liu
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan.|Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Tse-Hua
authors.initials: TH
authors.lastname: Tan
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan, Taiwan.|Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ting-Tsung
authors.initials: TT
authors.lastname: Chang
mesh_terms: D000368:Aged; D015551:Autoimmunity; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D053208:Kaplan-Meier Estimate; D016086:Lentivirus; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000473:pathology; D016016:Proportional Hazards Models; D064546:Protein Kinase C beta / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; C543044:MAP4K3 protein, human; D017346:Protein Serine-Threonine Kinases; D064546:Protein Kinase C beta
keywords: GLK; NFκB; hepatocellular carcinoma; recurrence