Elevated Expression of the Stem Cell Marker CD133 Associated with Line-1 Demethylation in Hepatocellular Carcinoma
Elevated Expression of the Stem Cell Marker CD133 Associated with Line-1 Demethylation in Hepatocellular Carcinoma
复制标题
肝细胞癌中与 Line-1 去甲基化相关的干细胞标记 CD133 表达升高
DOI：
10.1245/s10434-011-1599-1
复制
发表时间：
2011-08-01
影响因子：
3.7
通讯作者：
Wei, Lixin
中科院分区：
文献类型：
--
作者：
Zhang, Changsong;Xu, Yun;Wei, Lixin
目的探讨肝细胞癌（HCC）中Line-1去甲基化与肿瘤干细胞CD 133表达的关系。方法采用实时定量甲基化特异性聚合酶链反应（PCR）技术检测95例HCC及癌旁正常肝组织中Line-1甲基化水平，应用实时荧光定量逆转录聚合酶链反应（RT-PCR）和免疫组化方法检测CD 133的表达。Line-1的甲基化水平从癌旁组织（1.23 × 107 copies/μ gDNA）向肝癌组织（2.99 × 107 copies/μ gDNA）逐渐升高，但在肝癌和癌旁组织中，Line-1的甲基化水平保持在2 × 108 copies/μ gDNA左右。Line-1的甲基化指数（MI）从非肿瘤样品中的0.919降低到HCC中的0.755。结果显示，MI < 0.76的HCC患者的累积生存期明显短于MI ≥ 0.76的患者。CD 133 mRNA在HCC组织中的表达（平均− Ct= −5.751）高于非肿瘤组织（平均− Ct= −6.742）。共有73例（76.8%）患者发生Line-1去甲基化（AMI < 0），22例（23.2%）患者发生Line-1高甲基化（AMI ≥ 0）。肝癌与线-1去甲基化有升高的CD 133表达在肿瘤中，而不是匹配的非肿瘤组织（平均− T细胞Ct= 1.101），但肝癌与线-1高甲基化被认为是较低的CD 133表达在肿瘤中（平均− T细胞Ct=-0.409.ConclusionsLine-1低甲基化是在致癌过程中最常见的分子异常。HCC中CD 133的高表达与Line-1的去甲基化相关。
BackgroundThe relationship of Line-1 demethylation and the CD133 expression of cancer stem cells were discussed in hepatocellular carcinoma (HCC).MethodsIn 95 HCC and matched nontumor tissues, we analyzed the methylation level of Line-1 by quantitative real-time methylation-specific polymerase chain reaction, and the expression of CD133 by real-time reverse transcriptase–polymerase chain reaction and immunohistochemistry.ResultsUnmethylation of Line-1 increased from nontumor tissues (1.23 × 107copies/μg DNA) toward HCC tissues (2.99 × 107copies/μg DNA), but methylation of Line-1 kept 2 × 108copies/μg DNA around in HCC and nontumor tissues. The methylation index (MI) of Line-1 decreased from 0.919 in nontumor samples to 0.755 in HCC. Results showed that cumulative survival was significantly shorter in HCC patients with MI < 0.76 than that in patients with MI ≥ 0.76. CD133 mRNA expression were higher in HCC tissues (mean −∆Ct= −5.751) than that in nontumor tissues (mean −∆Ct= −6.742). A total of 73 (76.8%) patients had demethylation of Line-1 (∆MI < 0), and 22 (23.2%) patients had hypermethylation of Line-1 (∆MI ≥ 0). HCC with demethylation of Line-1 had elevated CD133 expression in tumor rather than matched nontumor tissues (mean −∆∆Ct= 1.101), but HCC with hypermethylation of Line-1 was considered to be lower with CD133 expression in tumor (mean −∆∆Ct= −0.409).ConclusionsLine-1 hypomethylation is the most common molecular abnormality during the carcinogenic process. Elevated expression of CD133 was associated with demethylation of Line-1 in HCC.