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Annals of Surgical Oncology

, Volume 18, Issue 2, pp 572–579 | Cite as

Reduced Expression of Reelin (RELN) Gene Is Associated With High Recurrence Rate of Hepatocellular Carcinoma

  • Yukiyasu Okamura
  • Shuji Nomoto
  • Mitsuro Kanda
  • Masamichi Hayashi
  • Yoko Nishikawa
  • Tsutomu Fujii
  • Hiroyuki Sugimoto
  • Shin Takeda
  • Akimasa Nakao
Translational Research and Biomarkers

Abstract

Background

Hepatocellular carcinoma (HCC) is one of the world’s top five causes of cancer-related deaths. Current treatments available ameliorate HCC; however, current therapy fails to completely treat and prevent HCC, as shown by its high recurrence rate. Recently developed genome-wide gene-expression profile analyses can now robustly detect many candidate genes that are modified by HCC. Here we attempt to identify novel genes displaying altered gene expression profiles when comparing healthy tissue with HCC by means of a double-combination array previously developed.

Methods

Double-combination array analysis of gene expression profiles and single nucleotide polymorphism arrays were performed on each HCC tissue sample. Subsequently, samples from 48 HCC patients were subjected to quantitative real-time reverse transcription polymerase chain reaction and methylation-specific polymerase chain reaction.

Results

The reelin (RELN) gene was detected as a pertinent tumor suppressor gene by means of this method. Of the 48 clinical samples obtained, 34 (79.2%) displayed reduced RELN expression in tumor tissue, and the expression level of tumor tissues clearly reduced compared with that of corresponding normal tissues (P = 0.002). Eighteen (37.5%) of 48 tumor tissues were found to be hypermethylated on the RELN gene promoter. Moreover, analysis of clinical data revealed an inverse correlation between RELN expression and HCC recurrence.

Conclusions

The present study indicates that our in-house double-combination array is an effective and convenient technique in detecting novel genes with altered expression in disease. We suggest RELN is a key regulatory gene associated with the recurrence of HCC.

Keywords

Single Nucleotide Polymorphism Promoter Hypermethylation Leukemia Inhibitory Factor Receptor RELN Gene Single Nucleotide Polymorphism Array 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Society of Surgical Oncology 2010

Authors and Affiliations

  • Yukiyasu Okamura
    • 1
  • Shuji Nomoto
    • 1
  • Mitsuro Kanda
    • 1
  • Masamichi Hayashi
    • 1
  • Yoko Nishikawa
    • 1
  • Tsutomu Fujii
    • 1
  • Hiroyuki Sugimoto
    • 1
  • Shin Takeda
    • 1
  • Akimasa Nakao
    • 1
  1. 1.Department of Surgery II, Graduate School and MedicineUniversity of NagoyaNagoyaJapan

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