Musashi-1在肝细胞肝癌中的表达及其与临床预后的关系

Expression of Musashi-1 in hepatocellular carcinoma and its relationship with clinical prognosis

目的研究Musashi-1在肝细胞肝癌患者癌组织及癌旁组织中的表达,探讨其与临床预后的关系及对肝癌细胞转移侵袭的影响。方法收集我院2000年6月至2010年6月间138例行根治性肝细胞肝癌切除术患者的术中肝癌以及癌旁样本,利用免疫组织化学方法检验癌组织与癌旁组织中Musashi-1的表达水平;通过Pearsonχ2检验和Fisher精确检验分析Musashi-1与患者临床特征以及预后之间的关系。利用qPCR检测癌组织和癌旁组织中CD133的表达并对癌组织中Musashi-1与CD133的表达水平进行相关性分析。构建稳定过表达Musashi-1的人肝癌细胞系SMMC-7721细胞,利用Sphere成球实验检测Musashi-1对肿瘤细胞成球能力的影响,利用肿瘤侵袭实验探究Musashi-1对肿瘤细胞侵袭能力的影响。结果 138例肝细胞肝癌患者中有105例(76.1%)癌组织中Musashi-1的表达高于癌旁组织(P<0.05)。Musashi-1的表达与甲胎蛋白(AFP)水平、腹水、远处转移有关(P<0.05),而与性别、年龄、乙肝病史、肿瘤大小、子灶、门静脉癌栓、镜下癌栓等无关。Musashi-1的表达水平对患者总体生存率和无瘤生存率有显著影响(P<0.05)。肝癌组织中CD133mRNA的表达高于癌旁组织(P<0.05),且CD133的表达与Musashi-1的表达呈正相关(R2=0.78,P<0.001)。体外实验证实过表达Musashi-1的SMMC-7721细胞的成球能力和侵袭能力增强。结论 Musashi-1在肝细胞肝癌中表达增加,对肝细胞肝癌的进展可能具有促进作用,其表达水平可以为判断预后提供参考。

ObjectiveTo study the expression of Musashi-1in tumor tissues and adjacent non tumor tissues of patients with hepatocellular carcinoma(HCC),and to explore the relationship between Musashi1and clinical prognosis and the effect of Musashi-1on the metastasis and invasion of HCC cells.MethodsWe collected HCC tissues and adjacent non tumor tissues from138patients undergoing radical resection of HCC in our hospital from June2000to June2010.The expression of Musashi-1in all tissues was detected by immunohistochemical method.The relationship between Musashi-1expression and clinical characteristics and prognosis was analyzed by Pearsonχ2test and Fisher exact test.The expression of CD133in HCC tissues and adjacent non tumor tissues was detected by qPCR and the correlation between Musashi-1and CD133in tumor tissues was analyzed.Finally,we constructed SMMC-7721cells with stable overexpression of Musashi-1,determined the effect of Musashi-1on the sphere forming potential of SMMC-7721cells using Sphere formation assay,and detected the effect of Musashi1on the ability of cell invasion by tumor invasion experiment.ResultsMusashi-1was highly expressed in105(76.1%)HCC tissues compared with the adjacent non tumor tissues(P<0.05).The expression of Musashi-1was related toαfetoprotein(AFP)level,ascites and distant metastasis(all P<0.05),but not to gender,age,HBV contagious history,tumor size,tumor foci,portal vein tumor thrombus or microscopic tumor thrombus(P>0.05).Spearman analysis indicated that HCC patients with higher Musashi-1expression have significantly worse overall survival rate(P<0.05)and disease free survival(P<0.05)compared with those with low Musashi1expression.The expression of CD133mRNA in HCC tissues was significantly higher than that in the adjacent non tumor tissues(P<0.05),and CD133expression was positively correlated with Musashi1expression(R2=0.78,P<0.001).In vitro experiments confirmed that overexpression of Musashi1enhanced the sphere forming potential and invasive ability of SMMC7721cells.ConclusionMusashi1has higher expression in HCC tissues and may promote HCC progression and metastasis.High level of Musashi1may indicate poor prognosis,providing a reference for prognosis judgment in HCC patients.