Promoter hypomethylation of protease-activated receptor 2 associated with carcinogenesis in the stomach.
OBJECTIVE
Trypsin acting at protease-activated receptor 2 (PAR2) contributes to a progression of malignant tumors. An abnormal DNA methylation has been recognized as an important molecular mechanism for the genesis of various types of cancers. We attempted to clarify the relationship between the promoter methylation of PAR2 and gastric cancer.


METHODS
We estimated the methylation of the PAR2 promoter in both antral non-cancerous mucosa and cancer lesions in 94 patients with gastric cancer. We employed a methylation-specific PCR method.


RESULTS
Regarding the methylation ratio (MR) of antral-non-cancerous mucosa, no significant difference was despite among gender, age and Helicobacter pylori infection status, whereas MR increased rising inflammation scores. The MR of cancer lesions was significantly lower than that of antral non-cancerous mucosa. This finding was not dependent on tumor staging, but also histological classification. In venous invasion, lymph node metastasis, or peritoneal dissemination negative cases, this significant lower MR was also seen.


CONCLUSIONS
The promoter methylation of PAR2 seems to be increased with a progression of chronic inflammation and has an inhibitory effect on carcinogenesis of the stomach.
Arisawa
Tomiyasu
T
Department of Gastroenterology, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan. tarisawa@fujita-hu.ac.jp
Tahara
Tomomitsu
T
Shibata
Tomoyuki
T
Nagasaka
Mitsuo
M
Nakamura
Masakatsu
M
Kamiya
Yoshio
Y
Fujita
Hiroshi
H
Takagi
Tamaki
T
Hasegawa
Shin
S
Wang
Fang-Yu
FY
Hirata
Ichiro
I
Nakano
Hiroshi
H
D000704:Analysis of Variance; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000201:enzymology / Q000235:genetics; D011401:Promoter Regions, Genetic; D044462:Receptors, Proteinase-Activated / Q000235:genetics*; D018709:Statistics, Nonparametric; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics*
D044462:Receptors, Proteinase-Activated