DKK-1和NNMT与肝癌患者临床病理指标及预后的相关性

Involvement of DKK-1 and NNMT in clinicopathology and prognosis among liver cancer patients

目的:探讨Dickkopf相关蛋白1(DKK-1)、尼克酰胺-N-甲基转移酶(NNMT) mRNA和蛋白表达与肝癌患者临床病理指标和预后的关系。方法:通过GEPIA2数据库分析NNMT和DKK-1 mRNA在正常肝组织和肝癌中的表达水平,分析两者对肝癌患者总生存期(OS)和无疾病生存期(DFS)的影响。采用免疫组织化学方法检测NNMT和DKK-1蛋白在肝癌、肝良性病变及正常组织中的表达情况,分析其与肝癌发生发展及临床病理指标间的关系。结果:GEPIA2数据库的分析结果显示,在肝癌组织中NNMT mRNA的表达水平明显低于正常肝组织(P<0.05),NNMT和DKK-1 mRNA在肝癌中的表达呈负相关关系(r=-0.13,P<0.05),两者对肝癌患者的10年OS及DFS均无明显影响。NNMT mRNA高表达的肝癌患者5年生存率比低表达者高(P<0.05)。免疫组织化学法检测结果发现与正常肝组织比较,DKK-1与NNMT蛋白在肝癌组织中的表达明显降低(P<0.01),DKK-1蛋白在肝细胞癌中的表达明显高于胆管细胞癌,两者的表达与肿瘤大小、分期及组织分级等无明显相关(P>0.05)。结论:DKK-1和NNMT蛋白在肝癌组织中的表达水平较正常肝组织下降,DKK-1蛋白的表达水平与肝癌的组织类型有关,NNMT mRNA的表达水平可能影响肝癌患者的5年生存率。

OBJECTIVE:To investigate the involvement of Dickkopf related protein 1(DKK-1)and nicotinamide N-methyltransferase(NNMT)in clinicopathology and prognosis among liver cancer patients.METHODS:Expression levels of NNMT and DKK-1 mRNA in normal liver tissues and liver cancer cells were analyzed by GEPIA2 database.,Effects of the two on the overall survival(OS)and disease-free survival(DFS)of patients with liver cancer were analyzed.Immunohistochemistry was used to detect the protein expression of NNMT and DKK-1 in liver tumor group,benign lesion group and normal group,and the relationship between them and the occurrence and development of liver cancer and clinicopathological features was analyzed.RESULTS:The GEPIA2 database showed that expression levels of NNMT mRNA in liver cancer tissues were significantly lower than that in normal liver tissues(P<0.05).Expressions of NNMT and DKK-1 mRNA in liver cancers were negatively correlated(r=-0.13,P<0.05).Both had no significant effect on the 10-year OS and DFS of liver cancer patients.The 5-year survival rate of liver cancer patients with high expression of NNMT mRNA was higher than that of those with low expression(P<0.05).The results of immunohistochemistry showed that compared with normal liver tissues,the expressions of DKK-1 and NNMT proteins in liver cancer tissues were significantly reduced(P<0.01).Expression of DKK-1 protein in hepatocellular carcinoma was significantly higher than that in cholangiocarcinoma.The expression of both proteins was not significantly correlated with tumor size,stage and tissue grade(P>0.05).CONCLUSION:The expression levels of DKK-1 and NNMT proteins in liver cancer tissues are lower than those in normal liver tissues.The expression levels of DKK-1 protein were related to the tissue types of liver cancers,and the expression levels of NNMT mRNA affected the 5-year survival rate of patients with liver cancer.