质子泵抑制剂治疗对Barrett食管APC基因启动子区甲基化的影响

背景：Barrett食管（BE）是食管腺癌的癌前病变，与食管腺癌的发生密切相关，已成为近年来的研究热点。目的：观察质子泵抑制剂（PPI）埃索美拉唑对BE患者抑癌基因APC表达及其启动子区甲基化的影响。方法：以甲基化特异性聚合酶链反应（PCR）和实时荧光定量PCR观察69例BE患者APC基因启动子区甲基化阳性率和APCmRNA表达在埃索美拉唑治疗前后的变化。分析治疗前APC基因启动子区甲基化状态与BE临床病理特征的关系。结果：埃索美拉唑治疗前，APC基因启动子区甲基化阳性率显著高于治疗后（42．0％对17．4％，P=0．007）。治疗前．长段BE的APC甲基化阳性率显著高于短段BE（46．8％对31．8％，P=0．032）；内镜下食管炎洛杉矶分类A级和B级者的APC甲基化阳性率显著低于C级和D级（19．0％对52．1％，P=0．046）；Ⅰ、Ⅱ、Ⅲ型BE间APC甲基化阳性率无明显差异（P=0．061）。埃索美拉唑治疗后，BE上皮APCmRNA表达量较治疗前显著增加（19．5±0．4对6．5±2．3，P=0．000）。结论：埃索美拉唑可抑制BE患者APC基因启动子区甲基化，增加抑癌基因APC表达。

Influence of Proton Pump Inhibitor on APC Gene Promoter Methylation in Barrett's Esophagus

Background： Barrett＇s esophagus （BE） is the precancerous lesion of esophageal adenocarcinoma, and is the hotspot of studies in recent years. Aims： To investigate the influence of esomeprazole, a proton pump inhibitor （PPI）, on the expression and promoter methylation of anti-oncogene APC in BE patients. Methods： APC gene promoter methylation rate was determined by methylation-specific poiymerase chain reaction （PCR） and APC mRNA expression was measured by real-time fluorescent quantitative PCR in 69 BE patients before and after esomeprazole treatment. The relationship between methyiation status of APC gene promoter and clinicopathological characteristics of BE before treatment was analyzed. Results： The positivity rate of APC gene promoter methylation before esomeprazole treatment was much higher than that after treatment （42.0% vs. 17.4%, P=0.007）. Before treatment, the positivity rate of APC gene promoter methylation in long-segment BE was significantly higher than that in short-segment BE （46.8% vs. 31.8%, P=-0.032）; the positivity rate of APC gene promoter methylation in A and B grades of Los Angeles Classification was much lower than that in C and D grades （19.0% vs. 52.1%, P=-0.046）; while there was no significant difference of the positivity rate of APC gene promoter methylation in three different BE types （P=0.061）. The average quantities of APC mRNA in Barrett＇s epithelium before and after esomeprazole treatment were 6.5±2.3 and 19.5±0.4, respectively; there was an obvious increase after esomeprazole treatment （P=0.000）. Conclusions： Esomeprazole may inhibit APC gene promoter methylation of BE and can increase the expression of anti-oncogene APC.