环氧化酶-2基因启动子甲基化及表达与胃黏膜病变的关系

目的 探讨环氧化酶2(COX-2)基因启动子区甲基化水平和蛋白表达与胃黏膜病变的关系,并对其相关的影响因素进行研究.方法 以1201例患有不同胃黏膜病变的高危人群为研究对象,采用免疫组织化学方法榆测COX-2表达,用亚硫酸氢钠-变性高效液相色谱(DHPLC)对COX-2启动子甲基化率进行定量分析,采用13C尿素呼气实验(13C-UBT)对幽门螺旋杆菌(H priori)感染状况进行测定.结果 COX-2甲基化率中位数随胃黏膜病变的加重逐渐升高,在浅表性胃炎和慢性萎缩性胃炎(SG/CAG)、肠上皮化生(IM)及不确定性异型增生和异璎增生(Ind DYS/DYS)病变中分别为10.6%、11.8%、13.8%,各病变组之间差异有统计学意义(X2=8.312,P=0.016).分层分析显示,在H pylori感染阴性病例中,COX-2甲基化率仍随病变加重明显升高,在SG/CAG、IM、Ind DYS/DYS病变中其中位数分别为8.8%、10.6%、14.1%(X2=6.629,P=0.036).进一步分析发现,COX-2甲基化率随着COX-2表达强度的增强而降低,由COX-2弱阳性表达的13.3%降至强阳性表达的7.6%(X2=10.400,P=0.015).结论 COX-2启动子甲基化水平与胃黏膜病变程度及H pylori感染状况密切相关,并与COX-2表达强度呈负相关,说明COX-2启动子区异常甲基化可能在胃黏膜病变的演变过程中起重要作用.

Association between promoter methylation of cyclooxygenase-2 and expression, and precancerous gastric lesions in a high-risk population

Objective To evaluate the relationship between cyclooxygenase-2 (COX-2) methylation and expression, and precancerous gastric lesions. Methods Methylation status of COX-2 was evaluated by quantitative denaturing high performance liquid chromatograghy (DHPLC) in 1201 subjects with different gastric lesions. COX-2 expression was assessed by immunohistochemistry and Helicobacter pylori (H pylori)infection status was determined by13C-urea breath test (13C-UBT). Results The percent of COX-2 methylation was increased steadily with the severity of gastric lesions, showing 10. 6% of which with superficial gastritis/chronic atrophic gastritis (SG/CAG), 11.8% with intestinal metaplasia (IM) and 13. 8% with indefinite dysplasia/dysplasia (Ind DYS/DYS) (X2=8. 312, P=0. 016). Stratified analysis indicated that the percents of COX-2 methylation in subjects with H pylori negative still increased with the severity of gastric lesions,of 8. 8% in SG/CAG, 10. 6% in IM and 14. 1% in lnd DYS/DYS (X2=6. 629,P=0. 036). Moreover,the methylated proportion of COX-2 was negatively associated with the expression in gastric lesions, from 13. 3% with mild expression to 7. 6% with strong expression (X2=10. 400, P=0. 015). Conclusion Our findings indicated that COX-2 methylation was significantly associated with precancerous gastric lesions and H pylori infection, suggesting that promoter methylation of COX-2 might play an important role in the progression of gastric lesions.