Quintiles, Inc., Rockville, Maryland, USA.
Hepatol Res. 2007 Sep;37 Suppl 2:S110-4. doi: 10.1111/j.1872-034X.2007.00172.x.
Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) remains the most common form of HCC in large areas of Asia and Africa. It remains common even in some countries where hepatitis C virus (HCV)-associated HCC has become the predominant form, such as Japan. Integration of HBV in HCC DNA is found at random sites in the host genome in nearly all patients with HBV-associated HCC. It is not clear how often this integration results in insertional mutagenesis, but previously unknown growth regulating genes and cancer-associated genes have been found frequently near HBV integration sites in HCC in recent studies. In addition, HBV encodes a transactivating protein, the X protein, which could enable the randomly integrated HBV to alter the function of host genes that are not near the integration site. Mutations at two adjacent codons in HBV (1762(T)/1764(A) mutations) within the X gene are frequently found in HCC patients, and may play a role in the mutagenic or transactivational role of HBV in HCC. The presence of cirrhosis in most patients with HBV-associated HCC, and the presence of mutations in tumor suppressor genes in many, suggests that these are also factors in hepatocarcinogenesis. Few studies have examined the mutations of more than one gene in the same HCC patients. Fewstudies have evaluated the interactions between HBV mutations, host gene mutations, cirrhosis, and other potentially mutagenic stresses at the cellular level, with progression to HCC, and few studies have been conducted to determine whether these changes must accumulate in succession to lead to HCC. The recent availability of rapid sequencing methods and DNA microarray technologies has permitted expression profiling and permutation analysis of an array of genes to explore the pattern and succession of molecular changes leading to HBV-associated HCC. To date, these methods have been used to show patterns of molecular changes that differ in HBV-associated HCC (compared to HCV-associated HCC or to HCC in patients lacking either virus) and patterns that can predict survival (and hence may directly indicate different mechanisms of disease), and may soon make possible a universally accepted clinical classification scheme for HCC.
乙型肝炎病毒（HBV）相关的肝细胞癌（HCC）仍然是亚洲和非洲大部分地区最常见的 HCC 形式。即使在一些丙型肝炎病毒（HCV）相关 HCC 已成为主要形式的国家，如日本，它仍然很常见。在所有 HBV 相关 HCC 患者中，HBV 整合到 HCC DNA 中是随机发生在宿主基因组中的。目前尚不清楚这种整合导致插入突变的频率，但在最近的研究中，在 HCC 中 HBV 整合位点附近经常发现以前未知的生长调节基因和癌症相关基因。此外，HBV 编码一种反式激活蛋白，即 X 蛋白，它可以使随机整合的 HBV 改变整合位点附近非宿主基因的功能。HBV 基因中两个相邻密码子（X 基因中的 1762（T）/1764（A）突变）的突变在 HCC 患者中经常发现，并且可能在 HBV 在 HCC 中的致突变或反式激活作用中发挥作用。大多数 HBV 相关 HCC 患者存在肝硬化，许多患者存在肿瘤抑制基因的突变，这表明它们也是肝癌发生的因素。很少有研究检查同一 HCC 患者中多个基因的突变。很少有研究评估 HBV 突变、宿主基因突变、肝硬化和其他潜在致突变应激在细胞水平上与 HCC 进展的相互作用，也很少有研究确定这些变化是否必须连续积累才能导致 HCC。最近快速测序方法和 DNA 微阵列技术的出现，使得对一系列基因进行表达谱分析和排列分析成为可能，以探索导致 HBV 相关 HCC 的分子变化的模式和顺序。迄今为止，这些方法已用于显示 HBV 相关 HCC（与 HCV 相关 HCC 或缺乏这两种病毒的 HCC 相比）中不同的分子变化模式以及可以预测存活的模式（因此可能直接指示不同的疾病机制），并且可能很快使 HCC 的通用临床分类方案成为可能。
