T细胞因子3(TCF3)在肝癌中高表达并促进肝癌的侵袭和转移

T cell factor 3 (TCF3) is overexpressed in hepatocellular carcinoma and promotes their invasion and metastasis

目的探讨T细胞因子3(TCF3)在肝细胞肝癌组织中的表达情况及其与肝癌患者预后的相关性,探索TCF3对肝癌细胞侵袭、迁移和转移能力的影响。方法利用肿瘤公共数据库和免疫组织化学染色方法,检测TCF3在肝癌组织的mRNA和蛋白表达,同时分析TCF3表达与肝癌患者预后的关系。Western blot法检测不同人肝癌细胞系中的TCF3的表达情况,并通过慢病毒感染技术分别构建TCF3上调、下调稳转细胞系,采用Transwell^(TM)实验检测TCF3对肝癌细胞体外侵袭迁移能力的影响,采用裸鼠肝脏原位移植瘤转移实验探究TCF3对肝癌细胞体内转移能力的影响。结果肝癌组织TCF3 mRNA表达显著高于正常肝组织,且TCF3 mRNA的高表达与肝癌患者总体生存率的降低密切相关;在120例肝癌组织中,TCF3蛋白表达水平显著高于癌旁组织,并且TCF3表达阳性患者较阴性患者术后总体生存率显著降低,而术后复发率显著增高;体外Transwell^(TM)实验表明,上调PLC/PRF/5肝癌细胞中TCF3的表达水平能促进其侵袭迁移能力,而下调HCCLM3细胞中TCF3的表达水平则能抑制其侵袭迁移能力;裸鼠肝脏原位移植瘤转移实验表明,上调TCF3能促进PLC/PRF/5细胞的体内转移,下调TCF3则减弱HCCLM3细胞的体内转移能力。结论TCF3在肝癌中的表达显著升高,TCF3的高表达与肝癌患者不良预后密切相关,TCF3能够显著促进肝癌细胞的侵袭、迁移和转移。

Objective To investigate the expression of T cell factor 3(TCF3) in hepatocellular carcinoma(HCC), its correlation with the prognosis of HCC patients, and its effect on the invasion, migration, and metastasis of HCC cells. Methods The expression of TCF3 mRNA in HCC tissues was detected with tumor public databases and the expression of TCF3 protein in HCC specimens was detected by immunohistochemical staining. Correlation between TCF3 expression and HCC patients’ prognosis was analyzed. Western blot analysis was used to detect the expression of TCF3 in different human HCC cell lines, and lentivirus infection was conducted to construct TCF3-upregulated and TCF3-downregulated HCC cell lines. The effect of TCF3 on the invasion and migration of HCC cells was assessed by in vitro Transwell^(TM)assay, and in vivo intrahepatic tumor implantation models were established to evaluate the effect of TCF3 on the metastatic capacity of HCC cells. Results The expression of TCF3 mRNA was significantly higher in HCC tissues than that in normal liver tissues, and high expression of TCF3 mRNA was closely correlated with decreased overall survival rates of HCC patients. In 120 cases of HCC tissues, the protein level of TCF3 was significantly higher than that in adjacent nontumor tissues, and patients with positive TCF3 expression had a markedly decreased overall survival rate and a higher recurrence rate compared with patients with negative TCF3 expression. In vitro Transwell^(TM)assay indicated that TCF3 upregulation promoted the invasion and migration of PLC/PRF/5cells, whereas knockdown of TCF3 inhibited the invasion and migration abilities of HCCLM3 cells. Intrahepatic tumor implantation models showed that TCF3 upregulation promoted the metastasis of PLC/PRF/5 cells, while TCF3 knockdown weakened the metastatic capacity of HCCLM3 cells. Conclusion TCF3 expression is significantly upregulated in human HCC tissues, and high TCF3 expression predicts a poor prognosis of HCC patients. TCF3 markedly promotes the invasion, migration, and metastasis of HCC cells.