Compartmentalized evolution of hepatitis B virus contributes differently to the prognosis of hepatocellular carcinoma.

Abstract

Serum hepatitis B virus (HBV) mutations can predict hepatocellular carcinoma (HCC) occurrence. We aimed to clarify if HBV evolves synchronously in the sera, adjacent liver and tumors and predict HCC prognosis equally. A total of 203 HBV-positive HCC patients with radical hepatectomy in Shanghai, China, during 2011-15 were enrolled in this prospective study. Quasispecies complexity (QC) in HBV core promoter region was assessed using clone-based sequencing. We performed RNA sequencing on tumors and paired adjacent tissues of another 15 HCC patients and analyzed it with three public data sets containing 127 samples. HBV QC was positively correlated to APOBEC3s' expression level (r = 0.28, P < 0.001), higher in the adjacent tissues than in the tumors (P = 6.50e-3), and higher in early tumors than in advanced tumors (P = 0.039). The evolutionary distance between the sera-derived HBV strains and the tumor-derived ones was significantly longer than that between the sera-derived ones and the adjacent tissue-derived ones (P < 0.001). Multivariate Cox regression analyses indicated that high HBV QC in the sera predicted an unfavorable overall survival (P = 0.002) and recurrence-free survival (RFS; P = 0.004) in HCC, whereas, in the tumors, it predicted a favorable RFS (P < 0.001). APOBECs-related HBV mutations, including G1764A, were more frequent in the sera than in the adjacent tissues. High-frequent A1762T/G1764A in the sera predicted an unfavorable RFS (P < 0.001), whereas, in the tumors, it predicted a favorable RFS (P = 0.035). In conclusion, HBV evolves more advanced in the sera than in the tumors. HBV QC and A1762T/G1764A in the sera and tumors have contrary prognostic effects in HCC.

• Authors: Jianhua Yin, Xi Chen, Nan Li, Xuewen Han, Wenbin Liu, Rui Pu, Ting Wu, Yibo Ding, Hongwei Zhang, Jun Zhao, Xue Han, Hongyang Wang, Shuqun Cheng, Guangwen Cao
• Journal: Carcinogenesis (Carcinogenesis) Vol. 42 Issue 3 Pg. 461-470 (04 17 2021) ISSN: 1460-2180 [Electronic] England
• PMID: 33247709 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Antiviral Agents
• DNA, Viral

Topics

• Adult
• Antiviral Agents (therapeutic use)
• Carcinoma, Hepatocellular (blood, mortality, therapy, virology)
• DNA Mutational Analysis
• DNA, Viral (analysis, genetics, isolation & purification)
• Datasets as Topic
• Disease-Free Survival
• Female
• Follow-Up Studies
• Hepatectomy
• Hepatitis B virus (genetics, isolation & purification)
• Hepatitis B, Chronic (blood, mortality, therapy, virology)
• Humans
• Liver (pathology, surgery, virology)
• Liver Neoplasms (blood, mortality, therapy, virology)
• Male
• Middle Aged
• Mutation Rate
• Neoplasm Recurrence, Local (epidemiology, virology)
• Prognosis
• Prospective Studies
• Risk Assessment (methods)