Wang Dan, Cai Hao, Yu Wen-Bo, Yu Long
The State Key Laboratory of Genetics Engineering, Fudan University Shanghai, 200433, P.R. China.
Int J Clin Exp Pathol. 2014 Aug 15;7(9):5988-96. eCollection 2014.
Hepatocellular carcinoma (HCC) is one of the most malignant tumors worldwide, especially in Eastern China where HBV infection confirmed as the most important pathological element. HBV X gene, extremely easy to mutate and integrate into hepatocytes, plays a significant role in HBV infection and HCC development. We deduced that mutations of integrated HBx gene make transformation more malignant. The aim of the study was to investigate whether there were different mutation patterns between the HCC tissues and the pericarcinoma liver tissues (PCLT) from patients with HCC in Eastern China.
HBx genes extracted from 287 HCC tissue samples and 195 PCLT tissue samples were analyzed by sequence alignment and stratified analysis with the matched medical records.
Mutations occurred complicated and changeable in both HCC and PCLT. COOH-terminal truncation is more frequently found in HCC than PCLT (P < 0.05). There is no single site mutation of nucleic acid or amino acid makes distribution discrepancy between HCC and PCLT. Hydrophobic/hydrophilic character of amino acid of site 43, 47, 127, 131, 132 make distribution discrepancy between HCC and PCLT in men when stratified for gender (P < 0.05). Hydrophobic/hydrophilic character of amino acid of site 40 makes distribution discrepancy between HCC and PCLT in both male and female (P < 0.05). Hydrophobic/hydrophilic character of amino acid of site 47 and 127 make significant discrepancy among clinical stage I, II, III (P < 0.05).
During the infection and replication of HBV, HBx mutates to adjust itself to the hepatocyte and increase the carcinogenesis. COOH-terminal truncated HBX may play a stimulative role in HBV-related HCC carcinogenesis as well as hydrophobic/hydrophilic character changes in some specific amino acid sites.
肝细胞癌(HCC)是全球最恶性的肿瘤之一,尤其是在中国东部地区,乙肝病毒(HBV)感染被确认为最重要的病理因素。HBV X基因极易发生突变并整合到肝细胞中,在HBV感染和HCC发展中起重要作用。我们推测整合的HBx基因突变会使转化更具恶性。本研究的目的是调查中国东部HCC患者的HCC组织与癌旁肝组织(PCLT)之间是否存在不同的突变模式。
从287份HCC组织样本和195份PCLT组织样本中提取的HBx基因,通过序列比对和与匹配病历的分层分析进行分析。
HCC和PCLT中的突变发生复杂且多变。COOH末端截短在HCC中比在PCLT中更常见(P < 0.05)。没有单个核酸或氨基酸位点突变使HCC和PCLT之间的分布存在差异。当按性别分层时,第43、47、127、131、132位点氨基酸的疏水/亲水性特征使男性的HCC和PCLT之间存在分布差异(P < 0.05)。第40位点氨基酸的疏水/亲水性特征使男性和女性的HCC和PCLT之间存在分布差异(P < 0.05)。第47和127位点氨基酸的疏水/亲水性特征在临床I、II、III期之间存在显著差异(P < 0.05)。
在HBV感染和复制过程中,HBx发生突变以适应肝细胞并增加致癌作用。COOH末端截短的HBX可能在HBV相关HCC致癌过程中起促进作用,以及某些特定氨基酸位点的疏水/亲水性特征变化。