Wang Bao-Can, Guo Chang-Qing, Sun Chao, Sun Qiao-Ling, Liu Guo-Yong, Li Ding-Guo
Digestive Department, Xinhua Hospital, Shanghai Second Medical University, 1665 Kongjiang Road, Shanghai 200092, China.
World J Gastroenterol. 2005 Jun 7;11(21):3240-4. doi: 10.3748/wjg.v11.i21.3240.
To determine the correlation between methylation status of 5' CpG island of cyclooxygenase-2 (COX-2) gene and protein expression in gastric cancer tissues for distinguishing the molecular characters of gastric cancers.
Methylation status of 5' CpG island of COX-2 gene was studied by PCR amplification after HpaII and Hha I restrictive enzyme digestion; COX-2 expression was evaluated by immunohistochemical method.
Hpa II and HhaI site were all methylated in 12 normal gastric mucosa tissues, whereas they were demethylated in 77.27% (34/44) and 84.09% (37/44) gastric cancer tissues, respectively. Expression of COX-2 was detected in 68.18% (30/44) gastric cancer tissues, but no expression was found in normal gastric mucosa tissues. In gastric cancer tissues, COX-2 expression was correlated significantly with HpaII site demethylation (29/30 vs 5/14, P<0.001 and HhaI site demethylation (28/30 vs 9/14, P<0.05).
The demethylation of 5' CpG island of gene is necessary for COX-2 expression in human gastric cancer. The expression status of COX-2 may provide theoretical basis for COX-2 targeting gastric cancer treatments.
确定环氧化酶-2(COX-2)基因5'CpG岛甲基化状态与胃癌组织中蛋白表达之间的相关性,以区分胃癌的分子特征。
通过HpaII和HhaI限制性酶切后的PCR扩增研究COX-2基因5'CpG岛的甲基化状态;采用免疫组织化学方法评估COX-2表达。
12例正常胃黏膜组织中Hpa II和HhaI位点均甲基化,而在胃癌组织中分别有77.27%(34/44)和84.09%(37/44)发生去甲基化。68.18%(30/44)的胃癌组织中检测到COX-2表达,而正常胃黏膜组织中未发现表达。在胃癌组织中,COX-2表达与HpaII位点去甲基化(29/30对5/14,P<0.001)和HhaI位点去甲基化(28/30对9/14,P<0.05)显著相关。
基因5'CpG岛去甲基化是人类胃癌中COX-2表达所必需的。COX-2的表达状态可为以COX-2为靶点的胃癌治疗提供理论依据。