Aberrant methylation of the Ras-related Associated with Diabetes gene in human primary esophageal cancer

Zhe Jin, Xianling Feng, Qianhe Jian, Yulan Cheng, Yan Gao, Xiaojing Zhang, Liang Wang, Yuan Zhang, Weiling Huang, Xinmin Fan, Si Chen, Huimin Yu, Zhenfu Zhao, Ming Dong, Jie Liu, Yuriko Mori, Stephen J. Meltzer

Research output: Contribution to journalArticlepeer-review

Abstract

Background/Aim: Ras-related associated with diabetes (RRAD), a member of the Ras-related GTPase superfamily, is frequently methylated in several human cancers, though its methylation profile remains unclear in esophageal cancer. Materials and Methods: We examined RRAD promoter hypermethylation using real-time quantitative methylation-specific PCR in 229 primary human esophageal tissues of contrasting histological types. Results: RRAD hypermethylation showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) from esophageal adenocarcinoma (EAC) or normal esophagus (NE) (p<0.01 and p<0.01, respectively). RRAD normalized methylation values were significantly higher in ESCC (0.0242) than in NE (0.0057, p<0.05) or EAC (0.0139, p<0.01). RRAD hypermethylation frequency was also significantly higher in ESCC (23.1%) than in NE (0%, p<0.05) or EAC (5.4%, p<0.05). Conclusion: Promoter hypermethylation of RRAD is a frequent, tissue-specific event in ESCC, and is uncommon in EAC. The aberrant methylation of RRAD may be involved in the pathogenesis of a subset of ESCC, but not in EAC.

Original languageEnglish (US)
Pages (from-to)5199-5204
Number of pages6
JournalAnticancer research
Volume33
Issue number11
StatePublished - Nov 2013

Keywords

  • EAC
  • ESCC
  • Hypermethylation
  • RRAD

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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