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Elevated Expression of the Stem Cell Marker CD133 Associated with Line-1 Demethylation in Hepatocellular Carcinoma

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgment

This project was supported by the National Natural Science Foundation of China (No: 30700981, 30870974, 30801347, 30901722, 30921006, 81000970, 81030041); the National Key Sci-Tech Special Project of China (2008ZX10002-019, 2008ZX10002-025); the Key Basic Research Project of China (2010CB945600, 2011CB966200); Shanghai Science and Technology Development Funds (08XD14003, 10ZR1439900, 10ZR1439600, 10411963100); Technology Planning Project of Changzhou Municipality (CS2008214, CS20102021); and Changzhou Health Bureau for the Talents.

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Authors and Affiliations

  1. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China

    Changsong Zhang MD, Yun Xu MD, Jun Zhao MD, Guocheng Jiang MD, Rong Li MD, Mengchao Wu MD & Lixin Wei MD, PhD

  2. Department of Clinical Laboratory, Shanghai East Hospital, Tongji University Medical School, Shanghai, China

    Changsong Zhang MD & Lieying Fan MD

  3. Clinical Oncology Laboratory, Changzhou Tumor Hospital, Medical College of Suzhou University, Changzhou, China

    Changsong Zhang MD & Yang Ling MD

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  1. Changsong Zhang MD
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  2. Yun Xu MD
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Correspondence to Lixin Wei MD, PhD.

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Changsong Zhang, Yun Xu, Jun Zhao authors contributed equally to this work.

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Zhang, C., Xu, Y., Zhao, J. et al. Elevated Expression of the Stem Cell Marker CD133 Associated with Line-1 Demethylation in Hepatocellular Carcinoma. Ann Surg Oncol 18, 2373–2380 (2011). https://doi.org/10.1245/s10434-011-1599-1

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