Jia Jian'an, Li Huiming, Wang Hui, Chen Shipeng, Wang Mengmeng, Feng Huijuan, Gao Yuzhen, Wang Yunjiu, Fang Meng, Gao Chunfang
Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, PR China.
Department of Laboratory Medicine, 105th Hospital of PLA, Hefei 230031, PR China.
J Gen Virol. 2017 Jun;98(6):1399-1409. doi: 10.1099/jgv.0.000790. Epub 2017 Jun 22.
The aim of this study was to explore the relationship between hepatitis B virus (HBV) core antigen (HBc) mutations and the post-operative prognosis of HBV-related hepatocellular carcinoma (HCC). In total, 98 patients suffering from HBV-related HCC and treated with surgery were enrolled, with a 48 month follow-up. The preCore/Core region of the HBV genome from tumour tissue (TT) and paired adjacent non-tumour tissue (ANTT) of these patients was sequenced, and a phylogenetic tree was reconstructed. The correlations between the viral features and evolutionary divergence of preCore/Core amino acid sequences from 67 paired TTs and ANTTs were analysed. Cox proportional hazard model analysis was applied for post-operative hazard risk evaluation. Phylogenetic analysis revealed that all of the sequences were ascribed to genotype C. The evolutionary divergence of amino acid sequences from matched TTs and ANTTs was significantly negatively correlated with serum and intrahepatic HBV DNA levels. Multivariate analysis showed that the HBc E77 mutation was associated with shorter overall survival, and HBc S87 and P156 mutations were independent risk factors for relapse. Furthermore, in contrast to with patients without the S87 mutation, no correlation was observed between serum HBV DNA and intrahepatic HBV DNA in HCC patients with the S87 mutation. Analysis of the intrahepatic sequence may advance our understanding of viral status; thus, it is useful for prognosis prediction for HBV-related HCC.
本研究旨在探讨乙肝病毒（HBV）核心抗原（HBc）突变与HBV相关肝细胞癌（HCC）术后预后之间的关系。总共纳入了98例接受手术治疗的HBV相关HCC患者，并进行了48个月的随访。对这些患者肿瘤组织（TT）和配对的相邻非肿瘤组织（ANTT）的HBV基因组前核心/核心区域进行测序，并重建系统发育树。分析了67对TT和ANTT的前核心/核心氨基酸序列的病毒特征与进化分歧之间的相关性。应用Cox比例风险模型分析进行术后风险评估。系统发育分析表明，所有序列均归为C基因型。配对的TT和ANTT的氨基酸序列进化分歧与血清和肝内HBV DNA水平显著负相关。多变量分析表明，HBc E77突变与总生存期缩短相关，HBc S87和P156突变是复发的独立危险因素。此外，与无S87突变的患者相比，有S87突变的HCC患者血清HBV DNA与肝内HBV DNA之间未观察到相关性。肝内序列分析可能会增进我们对病毒状态的理解；因此，它对HBV相关HCC的预后预测有用。
