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   <subfield code="a">10.1245/s10434-011-1599-1</subfield>
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   <subfield code="a">Elevated Expression of the Stem Cell Marker CD133 Associated with Line-1 Demethylation in Hepatocellular Carcinoma</subfield>
   <subfield code="h">[Elektronische Daten]</subfield>
   <subfield code="c">[Changsong Zhang, Yun Xu, Jun Zhao, Lieying Fan, Guocheng Jiang, Rong Li, Yang Ling, Mengchao Wu, Lixin Wei]</subfield>
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   <subfield code="a">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&lt;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&lt;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.</subfield>
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   <subfield code="a">Zhang</subfield>
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   <subfield code="u">Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China</subfield>
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   <subfield code="u">Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China</subfield>
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   <subfield code="u">Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China</subfield>
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   <subfield code="u">Department of Clinical Laboratory, Shanghai East Hospital, Tongji University Medical School, Shanghai, China</subfield>
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   <subfield code="u">Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China</subfield>
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