Published in:
01-08-2011 | Translational Research and Biomarkers
Elevated Expression of the Stem Cell Marker CD133 Associated with Line-1 Demethylation in Hepatocellular Carcinoma
Authors:
Changsong Zhang, MD, Yun Xu, MD, Jun Zhao, MD, Lieying Fan, MD, Guocheng Jiang, MD, Rong Li, MD, Yang Ling, MD, Mengchao Wu, MD, Lixin Wei, MD, PhD
Published in:
Annals of Surgical Oncology
|
Issue 8/2011
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Abstract
Background
The relationship of Line-1 demethylation and the CD133 expression of cancer stem cells were discussed in hepatocellular carcinoma (HCC).
Methods
In 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.
Results
Unmethylation of Line-1 increased from nontumor tissues (1.23 × 107 copies/μg DNA) toward HCC tissues (2.99 × 107 copies/μg DNA), but methylation of Line-1 kept 2 × 108 copies/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).
Conclusions
Line-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.