- Nuclear Expression of Hepatitis B Virus X Protein Is Associated with Recurrence of Early-Stage Hepatocellular Carcinomas: Role of Viral Protein in Tumor Recurrence
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Jing Jin, Hae Yoen Jung, KyuHo Lee, Nam-Joon Yi, Kyung-Suk Suh, Ja-June Jang, Kyoung-Bun Lee
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J Pathol Transl Med. 2016;50(3):181-189. Published online April 17, 2016
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DOI: https://doi.org/10.4132/jptm.2016.03.18
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 Abstract
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- Background
Hepatitis B virus (HBV) plays well-known roles in tumorigenesis of hepatocellular carcinoma (HCC) in infected patients. However, HBV-associated protein status in tumor tissues and the relevance to tumor behavior has not been reported. Our study aimed to examine the expression of HBV-associated proteins in HCC and adjacent nontumorous tissue and their clinicopathologic implication in HCC patients.
Methods
HBV surface antigen (HBsAg), HBV core antigen (HBcAg), and HBV X protein (HBx) were assessed in 328 HBV-associated HCCs and in 155 matched nontumorous tissues by immunohistochemistry staining.
Results
The positive rates of HBsAg and cytoplasmic HBx staining in tumor tissue were lower than those in nontumorous tissue (7.3% vs. 57.4%, p < .001; 43.4% vs. 81.3%, p < .001). Conversely, nuclear HBx was detected more frequently in tumors than in nontumorous tissue (52.1% vs. 30.3%, p < .001). HCCs expressing HBsAg, HBcAg, or cytoplasmic HBx had smaller size; lower Edmondson-Steiner (ES) nuclear grade, pT stage, and serum alpha-fetoprotein, and less angioinvasion than HCCs not expressing HBV-associated proteins. Exceptionally, nuclear HBx-positive HCCs showed higher ES nuclear grade and more frequent large-vessel invasion than did nuclear HBx-negative HCCs. In survival analysis, only nuclear HBx-positive HCCs had shorter disease-free survival than nuclear HBx-negative HCCs in pT1 and ES nuclear grade 1–2 HCC subgroup (median, 126 months vs. 35 months; p = .015).
Conclusions
Our data confirmed that expression of normal HBV-associated proteins generally decreases in tumor cells in comparison to nontumorous hepatocytes, with the exception of nuclear HBx, which suggests that nuclear HBx plays a role in recurrence of well-differentiated and early-stage HCCs.
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Citations
Citations to this article as recorded by  - Tertiary Prevention of HCC in Chronic Hepatitis B or C Infected Patients
Wei Teng, Yen-Chun Liu, Wen-Juei Jeng, Chien-Wei Su
Cancers.2021; 13(7): 1729. CrossRef - Suppression of hepatitis b virus by a combined activity of CRISPR/Cas9 and HBx proteins
S. A. Brezgin, A. P. Kostyusheva, V. N. Simirsky, E. V. Volchkova, D. S. Chistyakov, D. S. Kostyushev, V. P. Chulanov
Russian Journal of Infection and Immunity.2019; 9(3-4): 476. CrossRef - Hepatitis B virus surface gene pre-S2mutant as a high-risk serum marker for hepatoma recurrence after curative hepatic resection
Chia-Jui Yen, Yu-Lin Ai, Hung-Wen Tsai, Shih-Huang Chan, Chia-Sheng Yen, Kuang-Hsiung Cheng, Yun-Ping Lee, Chia-Wei Kao, Yu-Chun Wang, Yi-Lin Chen, Cheng-Han Lin, Tsunglin Liu, Huey-Pin Tsai, Jen-Ren Wang, Ih-Jen Su, Wenya Huang
Hepatology.2018; 68(3): 815. CrossRef - Integrin α6 as an invasiveness marker for hepatitis B viral X-driven hepatocellular carcinoma
Yi Rang Kim, Mi Ran Byun, Jin Woo Choi
Cancer Biomarkers.2018; 23(1): 135. CrossRef
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