Association of hTcf-4 gene expression and mutation with clinicopathological characteristics of hepatocellular carcinoma

AIM:Hepatocellular carcinoma(HCC)is a significant healthproblem in China.But the molecular mechanisms of HCCremains unclear.APC/β-Catenin/Tcf signaling pathway,alsoknown as Wnt pathway,plays a critical role in thedevelopment and oncogenesis.As little is known about thealteration of human T-cell transcription factor-4(hTcf-4)genein HCC,it is of interest to study the expression and mutationof hTcf-4 gene in HCC and the relationship between hTcf-4gene and progression of HCC.METHODS: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 normalliver tissues.PCR-single strand conformation polymorphism(PCR-SSCP)method was used to detect the mutation ofhTcf-4 exons 1,4,9 and 15 in HCC.The correlation ofexpression and mutation of the hTcf-4 gene withclinicopathological characteristics of HCC was also analyzed.RESULTS:RT-PCR showed that the expression rate of hTcf-4 mRNA in HCC,para-cancerous tissues and normal livertissues was 90.6 %,71.9 % and 80 %,respectively.Thegene expression level in tumor was 0.71±0.13,much higherthan that in para-cancerous liver 0.29±0.05 and normal liver0.26±0.05(P<0.001),although there was no significantdifference in gene expression level between para-canceroustissues and normal liver(P>0.05).Furthermore,hTcf-4 geneexpression was closely associated with tumor capsule statusand intrahepatic metastasis of HCC.On SSCP,2 of 32 casesof HCC(6.25 %)displayed characteristic mutational mobilityshifts in exon 15 of the hTcf-4 gene.No abnormal shiftingbands were observed in para-cancerous tissues.CONCLUSION: 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.