Jiang Ying, Zhou Xin-Da, Liu Yin-Kun, Wu Xin, Huang Xiao-Wu
Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai 200032, China.
World J Gastroenterol. 2002 Oct;8(5):804-7. doi: 10.3748/wjg.v8.i5.804.
Hepatocellular carcinoma(HCC) is a significant health problem in China. But the molecular mechanisms of HCC remains unclear. APC/beta-Catenin/Tcf signaling pathway, also known as Wnt pathway, plays a critical role in the development and oncogenesis. As little is known about the alteration of human T-cell transcription factor-4 (hTcf-4) gene in HCC, it is of interest to study the expression and mutation of hTcf-4 gene in HCC and the relationship between hTcf-4 gene and progression of HCC.
Reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect the expression of hTcf-4 mRNA in 32 HCC and para-cancerous tissues and 5 normal liver tissues. PCR-single strand conformation polymorphism (PCR-SSCP) method was used to detect the mutation of hTcf-4 exons 1, 4, 9 and 15 in HCC. The correlation of expression and mutation of the hTcf-4 gene with clinicopathological characteristics of HCC was also analyzed.
RT-PCR showed that the expression rate of hTcf-4 mRNA in HCC, para-cancerous tissues and normal liver tissues was 90.6 %, 71.9 % and 80 %, respectively. The gene expression level in tumor was 0.71+/-0.13, much higher than that in para-cancerous liver 0.29+/-0.05 and normal liver 0.26+/-0.05 (P<0.001), although there was no significant difference in gene expression level between para-cancerous tissues and normal liver (P>0.05). Furthermore, hTcf-4 gene expression was closely associated with tumor capsule status and intrahepatic metastasis of HCC. On SSCP, 2 of 32 cases of HCC (6.25 %) displayed characteristic mutational mobility shifts in exon 15 of the hTcf-4 gene. No abnormal shifting bands were observed in para-cancerous tissues.
The high expression level of hTcf-4 in HCC, especially in tumors with metastasis, suggests that the over-expression of hTcf-4 gene may be closely associated with development and progression of HCC, but the mutation of this gene seemed to play less important role in this respect.
肝细胞癌（HCC）在中国是一个严重的健康问题。但其分子机制仍不清楚。APC/β-连环蛋白/Tcf信号通路，也称为Wnt通路，在肿瘤发生发展过程中起关键作用。由于对人T细胞转录因子4（hTcf-4）基因在HCC中的改变了解甚少，因此研究hTcf-4基因在HCC中的表达、突变情况以及hTcf-4基因与HCC进展之间的关系具有重要意义。
采用逆转录-聚合酶链反应（RT-PCR）法检测32例HCC组织、癌旁组织及5例正常肝组织中hTcf-4 mRNA的表达。采用PCR-单链构象多态性（PCR-SSCP）法检测HCC组织中hTcf-4基因外显子1、4、9和15的突变情况。分析hTcf-4基因的表达和突变与HCC临床病理特征的相关性。
RT-PCR结果显示，hTcf-4 mRNA在HCC组织、癌旁组织和正常肝组织中的表达率分别为90.6%、71.9%和80%。肿瘤组织中的基因表达水平为0.71±0.13，显著高于癌旁肝组织的0.29±0.05和正常肝组织的0.26±0.05（P<0.001），尽管癌旁组织与正常肝组织之间的基因表达水平无显著差异（P>0.05）。此外，hTcf-4基因表达与HCC的肿瘤包膜状态及肝内转移密切相关。在SSCP检测中，32例HCC中有2例（6.25%）在hTcf-4基因外显子15处出现特征性突变迁移条带。癌旁组织未观察到异常迁移条带。
hTcf-4在HCC中高表达，尤其是在有转移的肿瘤中，提示hTcf-4基因的过表达可能与HCC的发生发展密切相关，但该基因的突变在这方面似乎作用较小。
