幽门螺杆菌对胃癌前期阶段胃上皮DNA同源重组修复关键蛋白的影响

目的 通过检测胃癌前期阶段幽门螺杆菌（Helicobacter pylori，H. pylori）阳性和阴性患者胃黏膜组织中DNA损伤标志物H2AX及同源重组（homologous recombination，HR）修复关键蛋白MRE11、Rad51、CtIP表达水平，评价H. pylori感染在胃癌前期阶段对HR精确修复的影响。方法 选择2017年3月至9月行胃镜及病理检测的165例H. pylori阳性和阴性患者，取胃黏膜上皮组织，石蜡包埋切片，行HE染色，根据世界卫生组织标准和更新的悉尼标准，划分病理类型。然后应用免疫组织化学染色方法检测H. pylori和DNA损伤标记蛋白及HR修复关键蛋白表达水平，并行统计学分析。结果 胃黏膜上皮细胞中H2AX的表达，在CSG、CAG和IM阶段，H. pylori阳性组表达高于阴性组（Mann-Whitney U=1116.5，P=0.001；Mann-Whitney U=185.0，P=0.018；Mann-Whitney U=214.5，P=0.041），在Dys阶段，H. pylori阳性组和阴性组差异无统计学意义（Mann-Whitney U=35.5，P=0.964）；MRE11的表达，在CSG、CAG阶段，H. pylori阳性组表达高于阴性组（Mann-Whitney U=1117.0，P=0.001；Mann-Whitney U=201.0，P=0.002），在IM、Dys阶段，H. pylori阳性组和阴性组差异无统计学意义（Mann-Whitney U=171.0，P=0.568；Mann-Whitney U=41.5，P=0.616）；Rad51的表达，在CSG、IM阶段，H. pylori阳性组表达低于阴性组（Mann-Whitney U=490.0，P=0.002；Mann-Whitney U=73.0，P=0.007），在CAG、Dys阶段，H. pylori阳性组和阴性组差异无统计学意义（Mann-Whitney U=101.0，P=0.404；Mann-Whitney U=24.0，P=0.291）；CtIP的表达，在CSG、IM阶段，H. pylori阳性组表达低于阴性组（Mann-Whitney U=593.0，P=0.044；Mann-Whitney U=58.5，P=0.001），在CAG、Dys阶段，H. pylori阳性组和阴性组差异无统计学意义（Mann-Whitney U=84.0，P=0.136；Mann-Whitney U=18.5，P=0.102）。结论 在胃癌前期发展阶段，H. pylori感染导致人体胃上皮细胞DNA损伤，却抑制部分HR修复通道关键蛋白表达，从而可能抑制精确的HR修复，增加细胞恶变几率。

The impact of Helicobacter pylori infection on key proteins of homologous recombination repair in early stage of gastric cancer

Objective To evaluate the expression of DNA damage marker H2AX and key proteins of homologous recombination repair (MRE11, Rad51 and CtIP) in the early stage of gastric cancer. Methods The gastric mucosa was collected from 165 H. pylori positive and negative patients underwent gastroscopy and pathological examination from March 2017 to September 2017. Pathological diagnosis and classification were made according to the criteria of the World Health Organization and the updated Sydney system. The level of H. pylori and the expression of DNA damage markers and HR repair key proteins were detected by using immunohistochemistry. Results The expression of H2AX in H. pylori positive group was higher than in H. pylori negative group in CSG, CAG and IM stages (Mann-Whitney U=1116.5, P=0.001; Mann-Whitney U=185.0, P=0.018; Mann-Whitney U=214.5, P=0.041), but there was no significant difference between the two groups in Dys stage（Mann-Whitney U=35.5, P=0.964). For the expression of MRE11 in H. pylori positive group was higher than in H. pylori negative group in CSG and CAG stages (Mann-Whitney U=1117.0, P=0.001; Mann-Whitney U=201.0, P=0.002), but there was no significant difference between the two groups in IM and Dys stages (Mann-Whitney U=171.0, P=0.568; Mann-Whitney U=41.5, P=0.616). The expression of Rad51 in H. pylori negative group was higher than in Hp positive group in CSG and IM stages (Mann-Whitney U=490.0, P=0.002; Mann-Whitney U=73.0, P=0.007), but there was no significant difference between the two groups in CAG and Dys stages (Mann-Whitney U=101.0, P=0.404; Mann-Whitney U=24.0, P=0.291). The expression of CtIP in H. pylori negative group was higher than in Hp positive group in CSG and IM stages (Mann-Whitney U=593.0, P=0.044; Mann-Whitney U=58.5, P=0.001), but there was no significant difference between the two groups in CAG and Dys stages (Mann-Whitney U=84.0, P=0.136; Mann-Whitney U=18.5, P=0.102). Conclusion H. pylori infection induces DNA damage, but inhibits some key proteins of HR repair in the early stage of gastric cancer, which may inhibit the HR repair and further increase the malignant transformation.