HBV and HCC - 3 abstracts.

StephenW

World J Gastroenterol. 2011 Nov 28;17(44):4853-7.
Hepatitis B virus infection and the risk of hepatocellular carcinoma.
Tan YJ.
Source: http://www.ncbi.nlm.nih.gov/pubmed/22171125
Ya-Jun Tan, Department of Laboratory Medicine, The First Affiliated
Hospital, College of Medicine, Zhejiang University, Hangzhou 310003,
Zhejiang Province, China.

Abstract
Epidemiological studies have provided overwhelming evidence for a causal
role of chronic hepatitis B virus (HBV) infection in the development of
hepatocellular carcinoma (HCC). However, the pathogenesis of HBV infection
and carcinogenesis of HBV-associated HCC are still elusive. This review
will summarize the current knowledge on the mechanisms involved in
HBV-related liver carcinogenesis. The role of HBV in tumor formation
appears to be complex, and may involve both direct and indirect mechanisms.
Integration of HBV DNA into the host genome occurs at early steps of clonal
tumor expansion, and it has been shown to enhance the host chromosomal
instability, leading to large inverted duplications, deletions and
chromosomal translocations. It has been shown that the rate of chromosomal
alterations is increased significantly in HBV-related tumors. Prolonged
expression of the viral regulatory HBV x protein may contribute to
regulating cellular transcription, protein degradation, proliferation, and
apoptotic signaling pathways, and it plays a critical role in the
development of hepatocellular carcinoma.

StephenW

世界胃肠病学杂志。2011年11月28日;17（44）:4853- 7。
乙型肝炎病毒感染和肝癌的风险。
谭鹰击。
资料来源：http://www.ncbi.nlm.nih.gov/pubmed/22171125
雅谭军，实验室医学系附属第一
医院，医学院，浙江大学，杭州310003
中国浙江省。

摘要
流行病学研究提供了确凿证据的因果
慢性乙型肝炎病毒（HBV）感染在发展中的作用
肝细胞癌（HCC）。然而，乙肝病毒感染的发病机制
和乙肝相关肝癌发生仍然是可望而不可及。此意见
将总结现有的知识上参与的机制
HBV相关的肝脏致癌。乙肝病毒在肿瘤形成中的作用
似乎很复杂，可能涉及的直接和间接的机制。
整合到宿主基因组HBV DNA发生在克隆的早期步骤
肿瘤扩展，它已被证明是增强宿主染色体
不稳定，导致大倒重复，缺失和
染色体易位。它已被证明，染色体率
改建是在乙型肝炎病毒相关的肿瘤显著增加。长时间
监管乙肝病毒X蛋白的表达可能有助于
调节细胞转录，蛋白质降解，扩散和
凋亡的信号传导通路，中起着关键作用
肝癌的发展。

StephenW

PLoS One. 2011;6(12):e28798. Epub 2011 Dec 8.
Source: http://www.ncbi.nlm.nih.gov/pubmed/22174901
Genome-wide association study of hepatocellular carcinoma in southern
chinese patients with chronic hepatitis B virus infection.

Chan KY, Wong CM, Kwan JS, Lee JM, Cheung KW, Yuen MF, Lai CL, Poon RT,
Sham PC, Ng IO. SourceState Key Laboratory for Liver Research, The
University of Hong Kong, Hong Kong.
Abstract One of the most relevant risk
factors for hepatocellular carcinoma (HCC) development is chronic hepatitis
B virus (HBV) infection, but only a fraction of chronic HBV carriers
develop HCC, indicating that complex interactions among viral,
environmental and genetic factors lead to HCC in HBV-infected patients. So
far, host genetic factors have incompletely been characterized. Therefore,
we performed a genome-wide association (GWA) study in a Southern Chinese
cohort consisting of 95 HBV-infected HCC patients (cases) and 97
HBV-infected patients without HCC (controls) using the Illumina
Human610-Quad BeadChips. The top single nucleotide polymorphisms (SNPs)
were then validated in an independent cohort of 500 cases and 728 controls.
4 SNPs (rs12682266, rs7821974, rs2275959, rs1573266) at chromosome 8p12
showed consistent association in both the GWA and replication phases
(OR(combined)?=?1.31-1.39; p(combined)?=?2.71×10(-5)-5.19×10(-4);
PAR(combined)?=?26-31%). We found a 2.3-kb expressed sequence tag (EST) in
the region using in-silico data mining and verified the existence of the
full-length EST experimentally. The expression level of the EST was
significantly reduced in human HCC tumors in comparison to the
corresponding non-tumorous liver tissues (P<0.001). Results from sequence
analysis and in-vitro protein translation study suggest that the transcript
might function as a long non-coding RNA. In summary, our study suggests
that variations at chromosome 8p12 may promote HCC in patients with HBV.
Further functional studies of this region may help understand
HBV-associated hepatocarcinogenesis.

StephenW

公共科学图书馆之一。 2011; 6（12）：e28798。作者2011年12月8。
资料来源：http://www.ncbi.nlm.nih.gov/pubmed/22174901
肝癌全基因组关联研究在南部
中国与慢性乙型肝炎病毒感染患者。

陈肯塔基州，黄CM，关JS，李JM，张千瓦，元朗MF，赖CL，潘RT，
深水电脑，吴IO。 SourceState肝研究重点实验室，
香港大学，香港。抽象的，最相关的风险
肝细胞癌（HCC）发展的因素是慢性肝炎
乙型肝炎病毒（HBV）感染，但只有小部分慢性乙肝病毒携带者
发展肝癌，表明之间的病毒复杂的相互作用，
遗传和环境因素是导致肝癌的乙肝病毒感染患者。因此，
到目前为止，宿主遗传因素不完全的特点。因此，
我们进行了全基因组关联（GWA）在中国南方研究
95 HBV感染的HCC患者（例）和97组成的队列
HBV感染无肝癌患者（对照组），使用Illumina公司
Human610四BeadChips。最高的单核苷酸多态性（SNP）的
在500例和728控制的独立的队列，然后验证。
4单核苷酸多态性（rs12682266，rs7821974，rs2275959，rs1573266）在染色体8p12
同时，GWA和复制阶段表现出一致协会
？（或（合并）= 1.31-1.39，P（合并）= 2.71 × 10（-5）-5.19 × 10（-4）？;
（PAR结合）= 26-31％）。我们发现一个2.3 kb的表达序列标签（EST）
该地区使用的硅片数据挖掘和验证的存在
全长EST实验。的EST表达水平
在人肝癌肿瘤相比，显著减少
相应的非癌肝组织（P <0.01）。从序列的结果
分析和体外蛋白翻译研究表明，谈话内容
作为一项长期的非编码RNA的功能。总之，我们的研究表明
在染色体8p12变异可能促进肝癌与乙肝患者。
本地区进一步的功能研究可能有助于了解
乙肝病毒相关的肝癌。

StephenW

PLoS One. 2011;6(12):e28486. Epub 2011 Dec 8.
Source: http://www.ncbi.nlm.nih.gov/pubmed/22174818
Serum MicroRNAs as Biomarkers for Hepatocellular Carcinoma in Chinese
Patients with Chronic Hepatitis B Virus Infection.
Qi P, Cheng SQ, Wang H,
Li N, Chen YF, Gao CF. SourceDepartment of Laboratory Medicine, Second
Military Medical University, Eastern Hepatobiliary Hospital, Shanghai,
China.

Abstract
BACKGROUND: MicroRNAs (miRNAs) have been shown to anticipate great cancer
diagnostic potential. Recently, circulating miRNAs have been reported as
promising biomarkers for various pathologic conditions. The objective of
this study was to investigate the potential of serum miRNAs as novel
biomarkers for hepatocellular carcinoma (HCC).

METHODOLOGY/PRINCIPAL FINDINGS: THIS STUDY WAS DIVIDED INTO FOUR PHASES:
(I) Ten candidate serum miRNAs were detected by using real-time RT-PCR,
corresponding 10 HCC patients with chronic hepatitis B virus (HBV)
infection and 10 age- and sex-matched healthy subjects. (II) Marker
validation by real-time RT-PCR on HBV patients with (n?=?48) or without HCC
(n?=?48), and healthy subjects (n?=?24). (III) Marker detection by
real-time RT-PCR in sera from another 14 HCC patients before and 1 month
after surgical resection. (IV) We examined the correlation between the
expressions of candidate serum miRNAs with clinical parameters of HCC
patients. Although miR-222, miR-223 or miR-21 were significantly up- or
down-regulated between HCC patients and healthy controls, no significant
difference was observed in the levels of these miRNAs between HBV patients
without and with HCC. MiR-122 in serum was significantly higher in HCC
patients than healthy controls (p<0.001). More importantly, it was found
that the levels of miR-122 were significantly reduced in the post-operative
serum samples when compared to the pre-operative samples. Although serum
miR-122 was also elevated in HBV patients with HCC comparing with those
without HCC, the difference was at the border line (p?=?0.043).

CONCLUSIONS/SIGNIFICANCE: Our results suggest that serum miR-122 might
serve as a novel and potential noninvasive biomarker for detection of HCC
in healthy subjects, moreover, it might serve as a novel biomarker for
liver injury but not specifically for detection of HCC in chronic HBV
infection patients.

StephenW

公共科学图书馆之一。 2011; 6（12）：e28486。作者2011年12月8。
资料来源：http://www.ncbi.nlm.nih.gov/pubmed/22174818
作为在中国的肝癌的生物标志物的血清小分子RNA
慢性乙型肝炎病毒感染的患者。齐磷，郑倚，王华，
李宁，陈施雅风，高的CF。 SourceDepartment的医学实验室，二
军医大学东方肝胆医院，上海，
中国

摘要
背景：微RNA（miRNA）已被证明预测大癌症
诊断的潜力。最近，循环miRNA的报道
有前途的各种病理条件下的生物标志物。客观
本研究旨在探讨作为一种新型的血清miRNA的潜力
肝细胞癌（HCC）的生物标志物。

方法/主要结论：本研究分为四个阶段：
（一）通过实时RT - PCR检测，血清miRNA的十大候选人
10相应的肝癌患者与慢性乙型肝炎病毒（HBV）
感染和10年龄和性别匹配的健康受试者。 （二）标记
验证实时RT - PCR检测乙肝患者（N = 48）或不HCC
（N？= 48），和正常人（N？=？24）。 （三）标记检测
实时RT - PCR技术从另外14个肝癌患者血清中前1个月
手术切除后。 （四）我们审查之间的相关性
与肝癌的临床参数候选人血清miRNA的表达
患者。虽然miR - 222的中，miR - 223或miR - 21的显著向上或
下调肝癌患者和健康对照之间，没有显著
在乙肝患者之间的这些miRNAs水平差异
而与肝癌。血清中的miR - 122显着高于在肝癌
比健康对照组（P <0.001）。更重要的是，它被发现
miR - 122的水平在手术后均显着降低
手术前的样本相比，血清标本。虽然血清
miR - 122的HBV与肝癌与那些比较患者也升高
没有肝癌，所不同的是在边界线（P？= 0.043）。

结论/意义：我们的研究结果表明，血清中的miR - 122可能
作为一种新的和潜在的非侵入性的生物标志物检测肝癌
此外，在健康受试者中，它可能作为一种新的生物标志物
肝损伤，但不是专门针对慢性乙肝病毒检测肝癌
感染的病人。