Aberrant methylation of the Ras-related associated with diabetes gene in human primary esophageal cancer.
OBJECTIVE
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.


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).


CONCLUSIONS
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.
The Shenzhen University School of Medicine. 3688 Nanhai Ave, Rm 703, Nanshan, Shenzhen, Guangdong, People's Republic of China 518060. Tel: +86 075586671904, zhejin1995@yahoo.com.
Zhe
Z
Jin
Xianling
X
Feng
Qianhe
Q
Jian
Yulan
Y
Cheng
Yan
Y
Gao
Xiaojing
X
Zhang
Liang
L
Wang
Yuan
Y
Zhang
Weiling
W
Huang
Xinmin
X
Fan
Si
S
Chen
Huimin
H
Yu
Zhenfu
Z
Zhao
Ming
M
Dong
Jie
J
Liu
Yuriko
Y
Mori
Stephen J
SJ
Meltzer
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004947:Esophagus / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012372:ROC Curve; D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics*
C084355:RRAD protein, human; D018631:ras Proteins
EAC; ESCC; RRAD; hypermethylation