| 摘要: |
| 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 χ2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。 |
| 关键词: 肝肿瘤 肝细胞癌 Musashi-1 肿瘤干细胞 预后 肿瘤转移 |
| DOI：10.16781/j.0258-879x.2017.10.1231 |
| 投稿时间：2017-04-15修订日期：2017-06-29 |
| 基金项目:上海市优秀学科带头人计划（14XD1400100）. |
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| Expression of Musashi-1 in hepatocellular carcinoma and its relationship with clinical prognosis |
| LIU Chen,DONG Li-wei,PAN Yu-fei,TAN Ye-xiong* |
(Signal Transduction Laboratory, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
*Corresponding author) |
| Abstract: |
| 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 χ2 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. |
| Key words: liver neoplasms hepatocellular carcinoma Musashi-1 neoplastic stem cells prognosis neoplasm metastasis |
