The characteristic changes in hepatitis B virus x region for hepatocellular carcinoma: a comprehensive analysis based on global data.
The characteristic changes in hepatitis B virus x region for hepatocellular carcinoma: a comprehensive analysis based on global data.
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DOI：
10.1371/journal.pone.0125555
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kato N
中科院分区：
文献类型：
--
作者：
Li W;Goto K;Matsubara Y;Ito S;Muroyama R;Li Q;Kato N
B型肝炎病毒（HBV）X区（HBx）的突变在肝癌发生中起重要作用，但其结果仍存在争议。我们试图阐明HBV基因型C感染患者HBx中潜在的肝细胞癌（HCC）特征性突变，以及这些突变在不同疾病阶段和基因型中的分布。从在线全球HBV数据库中下载HBx序列进行筛选，然后根据诊断信息分为非HCC或HCC组。患者的年龄，性别，国家或地区，和病毒基因型的患者的数据也被提取。进行Logistic回归以评估突变对HCC风险的影响。1)从下载的5956个HBx序列中提取源自29个国家/地区的1115份人血清的全长HBx序列（HCC：161;非HCC：954）。C基因型在非肝癌中占40.6%（387/954），在肝癌中占89.4%（144/161）。2)16个核苷酸位点在C基因型HCC和非HCC组之间的分布差异有统计学意义。3)Logistic回归分析显示，突变A1383 C（OR：2.32，95% CI：1.34-4.01），R1479 C/T（OR：1.96，95% CI：1.05-3.64; OR：5.15，95% CI：2.53-10.48），C1485 T（OR：2.40，95% CI：1.41-4.08），C1631T（OR：4.09，95% CI：1.41-11.85），C1653T（OR：2.58，95% CI：1.59-4.19），G1719 T（OR：2.11，95% CI：1.19-3.73）和T1800 C（OR：23.59，95% CI：2.25-247.65）是C基因型HBV相关HCC的独立危险因素，在不同疾病阶段呈现不同的趋势。4)几个基因型C HCC风险突变预先存在，甚至作为主要类型，在早期疾病阶段与其他基因型。与HCC风险相关的突变主要位于HBx转录激活区、病毒启动子、蛋白/miRNA结合位点和免疫表位区域。此外，这些突变的特征是导致HCC的疾病阶段所特有的，表明在肝癌发生过程中病毒和宿主之间的分子对抗。
Mutations in hepatitis B virus (HBV) X region (HBx) play important roles in hepatocarcinogenesis while the results remain controversial. We sought to clarify potential hepatocellular carcinoma (HCC)-characteristic mutations in HBx from HBV genotype C-infected patients and the distribution of those mutations in different disease phases and genotypes. HBx sequences downloaded from an online global HBV database were screened and then classified into Non-HCC or HCC group by diagnosis information. Patients' data of patient age, gender, country or area, and viral genotype were also extracted. Logistic regression was performed to evaluate the effects of mutations on HCC risk. 1) Full length HBx sequences (HCC: 161; Non-HCC: 954) originated from 1115 human sera across 29 countries/areas were extracted from the downloaded 5956 HBx sequences. Genotype C occupied 40.6% of Non-HCC (387/954) and 89.4% of HCC (144/161). 2) Sixteen nucleotide positions showed significantly different distributions between genotype C HCC and Non-HCC groups. 3) Logistic regression showed that mutations A1383C (OR: 2.32, 95% CI: 1.34-4.01), R1479C/T (OR: 1.96, 95% CI: 1.05-3.64; OR: 5.15, 95% CI: 2.53-10.48), C1485T (OR: 2.40, 95% CI: 1.41-4.08), C1631T (OR: 4.09, 95% CI: 1.41-11.85), C1653T (OR: 2.58, 95% CI: 1.59-4.19), G1719T (OR: 2.11, 95% CI: 1.19-3.73), and T1800C (OR: 23.59, 95% CI: 2.25-247.65) were independent risk factors for genotype C HBV-related HCC, presenting different trends among individual disease phases. 4) Several genotype C HCC risk mutations pre-existed, even as major types, in early disease phases with other genotypes. Mutations associated with HCC risk were mainly located in HBx transactivation domain, viral promoter, protein/miRNA binding sites, and the area for immune epitopes. Furthermore, the signatures of these mutations were unique to disease phases leading to HCC, suggesting molecular counteractions between the virus and host during hepatocarcinogenesis.
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影响因子：
30.8
作者：
Sung, Wing-Kin;Zheng, Hancheng;Luk, John M.
通讯作者：
Luk, John M.
影响因子：
29.4
作者：
Kao, JH;Chen, PJ;Chen, DS
通讯作者：
Chen, DS
DOI：
10.1093/jnci/djp180
发表时间：
2009-08-05
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Liu S;Zhang H;Gu C;Yin J;He Y;Xie J;Cao G
通讯作者：
Cao G
影响因子：
29.4
作者：
Kao, JH;Chen, PJ;Chen, DS
通讯作者：
Chen, DS
影响因子：
12.7
作者：
Kim, Hyun-Ju;Park, Joo-Hee;Kim, Bum-Joon
通讯作者：
Kim, Bum-Joon