文章摘要
黄新立,高园园,丁 军,王学浩.原发性肝细胞肝癌组织中IMP3表达与临床特点和基因甲基化相关性的研究[J].南京医科大学学报,2014,(5):537~542
原发性肝细胞肝癌组织中IMP3表达与临床特点和基因甲基化相关性的研究
Correlation of genetic methylation with IMP3 expression and clinical features in primary hepatocellular carcinoma
投稿时间:2013-10-27  
DOI:10.7655/NYDXBNS20140501
中文关键词: 胰岛素样生长因子ⅡmRNA结合蛋白3  IMP3  原发性肝细胞肝癌  基因甲基化  启动子
英文关键词: insulin-like growth factorⅡ mRNA binding3  IMP3  hepatocellular carcinoma  HCC
基金项目:国家自然科学基金资助(81273262)
作者单位
黄新立 南京医科大学第一附属医院肝脏外科,江苏 南京 210029 
高园园 常州市第二人民医院普通外科,江苏 常州 213000 
丁 军 中山大学附属第一医院惠亚医院急诊科,广东 惠州 516081 
王学浩 南京医科大学第一附属医院肝脏外科,江苏 南京 210029 
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中文摘要:
      目的:研究IMP3在原发性肝细胞肝癌中的表达意义以及基因甲基化同IMP3表达的关系?方法:免疫组化检测162例肝细胞肝癌组织中IMP3的表达?分析临床因素与IMP3表达水平的相关性,并随访所选162例术后患者生存情况作生存分析?提取正常肝组织?肝癌组织的DNA,通过甲基化特异性定量PCR测定IMP3启动子CpG岛甲基化状态?培养正常肝脏细胞L02和Huh-7肝癌细胞,通过Western blot检测IMP3蛋白的表达?提取两组细胞DNA,分别对IMP3基因启动子区域CpG岛进行甲基化状态检测?结果:原发性肝细胞肝癌组织中IMP3阳性率为67.90%;IMP3表达与患者年龄?肿瘤大小?分级?分期?AFP?早期复发均存在相关性;而与性别?HBsAg无明显相关性?随访显示IMP3阳性患者长期生存明显低于IMP3阴性者?CpG岛甲基化检测显示肝癌组织中P1和P2位点高度去甲基化,而正常肝脏组织中P1和P2则处于甲基化状态?正常肝脏细胞IMP3表达阴性,Huh-7肝癌细胞IMP3表达强阳性?正常肝细胞P1和P2位点处于高度甲基化状态,而Huh-7肝癌细胞P1和P2位点处于去甲基化状态?结论:IMP3在原发性肝细胞肝癌中具有高表达,IMP3高表达提示不良预后;基因的甲基化同IMP3的表达存在一定的相关性?
英文摘要:
      Objective:To investigate the clinical significance of IMP3 expression, and to detect the relationship between IMP3 expression and genetic methylation. Methods:Paraffin sections of tumor tissues from 162 patients with HCC were examined for IMP3 expression by immunohistochemistry. Correlation analysis of clinical factors and IMP3 expression level was performed. One hundred and sixty-two patients with post-operation of HCC were follow-up for long-term survival analysis. P1 and P2 of IMP3 gene from normal and tumor tissues were detected by methylation-specific PCR and DNA sequencing. IMP3 protein was detected by Western Blot from cultured normal liver cells L02 and Huh7 hepatoma cells. DNA was extracted from two groups of cells,and the methylation status of promoter region CpG islands in IMP3 gene was detected. Results:IMP3 was expressed in 67.90% of HCC. IMP3 expression is related to age,tumor size, grading, staging,AFP,early relapse,but not gender and HBsAg. One hundred and sixty-two cases of postoperative follow-up found that postoperative long-term survival rate of IMP3 negative group was significantly higher than that of the IMP3-positive group(P < 0.01). Detection of P1 and P2 by methylation-specific PCR showed that CpG islands from P1 and P2 of tumor tissues showed unmethylated modification,however,those of normal tissues showed methylated modification. Normal liver cells were IMP3 negative,Huh-7 hepatoma cells showed strongly positive IMP3 expression. P1 and P2 of normal liver cells were highly methylated,and P1 and P2 of Huh-7 hepatoma cells showed unmethylated status. Conclusion:The level of IMP3 expression is high in HCC,and high IMP3 expression suggests poor prognosis;DNA methylated modification may participate in the processes,which regulates and controls IMP3 expression.
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