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Cell Physiol Biochem. 2018 Sep 7;49(3):1007-1018. doi: 10.1159/000493285. [Epub ahead of print]
Association of Low Zinc Finger Antiviral Protein Expression with Progression and Poor Survival of Patients with Hepatocellular Carcinoma.
Liu Y1,2, Hu C3, Zhu WB4, Xu WX1,2, Li ZY1,2, Lin Y4, Cai J4, Liang JK4, Zhu X1,2, Gao ZL1,2, Yan GM4,5, Peng L1,2.
Author information
1
Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
2
Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
3
Department of Urology Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
4
Departments of Pharmacology, Sun Yat-sen University, Guangzhou, China.
5
Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Abstract
BACKGROUND/AIMS:
Zinc finger antiviral protein (ZAP) has been reported to be expressed in hepatocellular carcinoma (HCC), and ZAP expression is associated with apoptotic signaling in cancer cells. This study aimed at investigating the expression of ZAP in HCC cells and its significance in clinical pathology.
METHODS:
Real-time quantitative PCR and western blot assays were employed to detect ZAP RNA and protein expression in normal human hepatocytes, HCC cells, and five primary HCC cell lines. Immunohistochemistry was performed to detect ZAP expression in 147 paraffin-embedded HCC tissues and adjacent normal tissues. The clinical significance of ZAP expression was analyzed in tissue samples from patients with or without infection by hepatitis B virus (HBV).
RESULTS:
ZAP expression in HCC cells and human primary HCC cell lines was significantly lower than that of normal human hepatocytes. Among 147 HCC samples, ZAP expression was lower in HCC tissues than in adjacent normal tissues for 107 (77.0%) samples. In patients with HCC and HBV infection, ZAP expression was related to pathological grade (P < 0.05); in HBV-negative patients with HCC, ZAP expression was associated with tumor size (P < 0.05) and clinical stage (P < 0.05). The overall survival time in patients with low ZAP expression was significantly shorter than survival times of those with high ZAP expression (P < 0.05), especially for patients with moderately to well-differentiated HCC (Grade 1-2) and HCC at stage T1 and T2 (P < 0.05). Cox multivariate analysis showed that ZAP expression was an independent predictor of survival of patients with HCC (P < 0.01).
CONCLUSION:
Low ZAP expression is closely associated with disease progression and poor prognosis for patients with HCC.
© 2018 The Author(s). Published by S. Karger AG, Basel.
KEYWORDS:
Biomarker; Hepatocellular carcinoma; Prognosis; ZAP; Zinc antiviral protein
PMID:
30196292
DOI:
10.1159/000493285 |
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