Musashi-1在肝细胞肝癌中的表达及其与临床预后的关系

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Pearson x2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CD133 mRNA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.

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

Objective To study the expression of Musashi-1 in tumor tissues and adjacent non-tumor tissues of patients with hepatocellular carcinoma (HCC),and to explore the relationship between Musashi-1 and clinical prognosis and the effect of Musashi-1 on the metastasis and invasion of HCC cells.Methods We collected HCC tissues and adjacent non-tumor tissues from 138 patients undergoing radical resection of HCC in our hospital from June 2000 to June 2010.The expression of Musashi-1 in all tissues was detected by immunohistochemical method.The relationship between Musashi-1 expression and clinical characteristics and prognosis was analyzed by Pearson x2 test and Fisher exact test.The expression of CD133 in HCC tissues and adjacent non-tumor tissues was detected by qPCR and the correlation between Musashi-1 and CD133 in tumor tissues was analyzed.Finally,we constructed SMMC-7721 cells with stable overexpression of Musashi-1,determined the effect of Musashi-1 on the sphere-forming potential of SMMC-7721 cells using Sphere formation assay,and detected the effect of Musashi-1 on the ability of cell invasion by tumor invasion experiment.Results Musashi-1 was highly expressed in 105 (76.1％) HCC tissues compared with the adjacent non-tumor tissues (P＜0.05).The expression of Musashi-1 was related to α-fetoprotein (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-1 expression have significantly worse overall survival rate (P＜0.05) and disease-free survival (P＜0.05)compared with those with low Musashi-1 expression.The expression of CD133 mRNA in HCC tissues was significantly higher than that in the adjacent non-tumor tissues (P＜0.05),and CD133 expression was positively correlated with Musashi-1 expression (R2 =0.78,P＜0.001).In vitro experiments confirmed that overexpression of Musashi-1 enhanced the sphere-forming potential and invasive ability of SMMC-7721 cells.Conclusion Musashi-1 has higher expression in HCC tissues and may promote HCC progression and metastasis.High level of Musashi-1 may indicate poor prognosis,providing a reference for prognosis judgment in HCC patients.