HBV mutations in EnhII/BCP/PC region contribute to the prognosis of hepatocellular carcinoma.

Zijun Ge,Zhibin Hu,Juncheng Dai,Ci Song,Jibin Liu,Xin Xu,Ting Tian,Lijuan Meng,Chengxiao Yu

doi:10.1002/cam4.2169

Abstract

BackgroundAccompanied by HBV infection, HBV mutations gradually occur because HBV polymerase appears proofread deficiencies. In our previous study, we have identified that EnhII/BCP/PC mutations and genotype C of HBV DNA were associated with hepatocellular carcinoma (HCC) risk. In this study, we extend our research to explore HCC prognosis associated genotype and mutations in EnhII/BCP/PC regions.MethodsWe designed a case‐cohort study of 331 HCC patients to evaluate the effects of the HBV genotypes and mutations on HCC survival. Log‐rank test and Cox proportional hazard models were used for the analyses.ResultsResults showed that genotype C, which was more frequent in HBV‐related HCC (77.4%), presented a negative signal with HCC survival. Interestingly, we detected a significant association between EnhII/BCP/PC mutation nt1753 and HCC prognosis (Log‐rank P = 0.034). Subgroup analysis revealed that this risk effect was more pronounced in non‐B genotype (P = 0.090 for heterogeneity test). We also detected a borderline multiplicative interaction between genotypes of nt1753 and HBV genotype on HCC survival (P for interaction = 0.069).ConclusionsThese findings indicated that, in Chinese population, nt1753 in EnhII/BCP/PC region might be a novel marker for HCC prognosis.

Highlights

Liver cancer ranged as the seventh most common cancer and the fourth leading cause of global cancer deaths
Multivariate Cox regression model was further applied to select HBV mutations which associated with hepatocellular carcinoma (HCC) survival, with adjustment––for age, sex, drinking and smoking status, chemotherapy or transcatheter hepatic arterial chemoembolization (TACE), and Barcelona Clinic Liver Cancer (BCLC) stage
Mutation nt1753 was associated with HCC prognosis (Log‐rank P = 0.034; hazard ratio. aAdjusted for age (HR) = 0.73, 95% confidence intervals (CI) = 0.55‐0.97, P = 0.035) (Table 3)

Summary

Funding information

This work was supported in part by the National Natural Science Foundation of China (81573238); the Outstanding youth Foundation of the Jiangsu Province (BK20160095); the National Natural Science Foundation of China (81402724, 81402741); the Natural Science Foundation of the Jiangsu Province (BK20140904); a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine); and Top‐notch Academic Programs Project of Jiangsu Higher Education Institutions (PPZY2015A067).

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