2022 年第 3 期 第 17 卷

硫氧还蛋白1 mRNA和精氨酸酶mRNA作为幽门螺杆菌高致病性标志物的应用价值

The value of thioredoxin-1 mRNA and arginase mRNA as highly pathogenic markers in Helicobacter pylori

作者：关馨1宁静1石岩岩2付伟伟1李炳庆3王磊3王学红4陈凤娟4张志广5李熳5孟杰6门路6隋淑静7李明7马颖才8袁玲8张静1丁士刚1

英文作者：Guan Xin1 Ning Jing1 Shi Yanyan2 Fu Weiwei1 Li Bingqing3 Wang Lei3 Wang Xuehong4 Chen Fengjuan4 Zhang Zhiguang5 Li Man5 Meng Jie6 Men Lu6 Sui Shujing7 Li Ming7 Ma Yingcai8 Yuan Ling8 Zhang Jing1 Ding Shigang1

单位：1北京大学第三医院消化科，北京100191；2北京大学第三医院临床流行病学研究中心，北京100191；3承德医学院附属医院消化科，承德067000；4青海大学附属医院消化科，西宁810012；5天津医科大学第二医院消化科，天津300211；6河北大学附属医院消化科，保定071000；7山东省泰安市中心医院食管胃肠内科，泰安271000；8青海省人民医院消化科，西宁810007

英文单位：

关键词：幽门螺杆菌；胃癌；硫氧还蛋白1；精氨酸酶

英文关键词：1DepartmentofGastroenterology,PekingUniversityThirdHospital,Beijing100191,China;2EpidemiologyCenter,PekingUniversityThirdHospital,Beijing100191,China;3DepartmentofGastroenterology,AffiliatedHospitalofChengdeMedicalUniversity,Chengde067000,China;4DepartmentofGastroenterology,QinghaiUniversityAffiliatedHospital,Xining810012,China;5DepartmentofGastroenterology,theSecondHospitalofTianjinMedicalUniversity,Tianjin300211,China;6DepartmentofGastroenterology,AffiliatedHospitalofHebeiUniversity,Baoding071000,China;7DepartmentofEsophagusandGastrointestinalInternalMedicine,TaianCentralHospital,ShandongProvince,Taian271000,China;8DepartmentofGastroenterology,QinghaiProvincialPeople′sHospital,Xining810007,China

• 摘要：

• 目的 探讨硫氧还蛋白1（Trx1）mRNA、精氨酸酶mRNA在幽门螺杆菌（Hp）感染的不同疾病胃窦组织中的表达量，分析二者作为Hp高致病性标志物的应用价值。方法  选取2020年9月至2021年7月于北京大学第三医院等7家医院接受内镜检查且Hp阳性的198例患者的胃窦组织，其中慢性胃炎 106例（慢性胃炎组）、溃疡病31例（溃疡病组）、胃癌61例（胃癌组）。另选取同期于北京大学第三医院接受内镜检查且Hp阴性的48例患者的胃窦组织。采用实时荧光定量聚合酶链反应测定Trx1 mRNA、精氨酸酶mRNA相对表达量。分析二者作为筛选高致病性Hp标志物及预测Hp感染者临床结局的价值。结果 Hp阴性胃窦组织中均未检出Trx1 mRNA、精氨酸酶mRNA表达。198例Hp阳性胃窦组织中均检出Trx1 mRNA，溃疡病组和胃癌组Trx1 mRNA相对表达量均高于慢性胃炎组［1.81(0.04,3.48)、0.51(0.21,2.80)比0.14(0.03,0.79)］（均P＜0.05）；149例检出精氨酸酶mRNA阳性，溃疡病组和胃癌组精氨酸酶mRNA相对表达量均高于慢性胃炎组［0.94(0.31,1.75)、1.78(0.42,3.21)比0.38(0.08,1.14)］（均P＜0.05）。受试者工作特征曲线分析结果显示，Trx1 mRNA筛选出高致病性Hp的曲线下面积为0.666、最佳截断值为1.95；精氨酸酶mRNA筛选出高致病性Hp的曲线下面积为0.642、最佳截断值为3.63。149例Trx1 mRNA、精氨酸酶mRNA表达的Hp阳性患者中，Trx1 mRNA+精氨酸酶mRNA串联预测溃疡病+胃癌的特异度、阳性预测值最高，误诊率最低；Trx1 mRNA+精氨酸酶mRNA并联预测溃疡病+胃癌的敏感度、阴性预测值最高，漏诊率最低。结论  Trx1 mRNA和精氨酸酶mRNA联合检测可用于筛选高致病性Hp，预测Hp感染结局。

• Objective   To explore expressions of thioredoxin-1 (Trx1) and arginase (RocF) mRNA in gastric antrum tissues of different diseases infected by Helicobacter pylori (Hp), and to analyze the application value of both indexes as highly pathogenic markers of Hp. Methods   From September 2020 to July 2021, gastric antrum tissues of 198 patients with Hp positive undergoing gastroscope in 7 hospitals including Peking University Third Hospital were enrolled. Among them, 106 cases had chronic gastritis (chronic gastritis group), 31 cases had ulcer (ulcer group) and 61 cases had gastric cancer (gastric cancer group). The gastric antrum tissues of 48 patients without Hp who underwent gastroscope in Peking University Third Hospital were enrolled. Relative expressions of Trx1 mRNA and RocF mRNA were detected by real-time fluorescence quantitative polymerase chain reaction. The value of both indexes as screening highly pathogenic Hp markers and predicting the clinical outcome of Hp infection were analyzed. Results  Trxl mRNA and RocF mRNA were not expressed in Hp negative gastric antrum tissues. Trx1 mRNA was expressed in 198 cases of Hp positive gastric antrum tissues, and the relative expression of Trx1 mRNA in ulcer group and gastric cancer group was higher than that in chronic gastritis group［1.81(0.04, 3.48), 0.51(0.21, 2.80) vs 0.14(0.03, 0.79)］(both P<0.05); RocF mRNA was expressed in 149 cases, and the relative expression of RocF mRNA in ulcer group and gastric cancer group was higher than that in chronic gastritis group［0.94(0.31, 1.75), 1.78(0.42, 3.21) vs 0.38(0.08, 1.14)］(both P<0.05). Receiver operating characteristic curve analysis showed that the area under the curve (AUC) for screening highly pathogenic Hp by Trx1 mRNA was 0.666 and the cut-off value was 1.95; AUC by RocF mRNA was 0.642 and the cut-off value was 3.63. Among 149 patients of Hp positive with Trx1 mRNA and RocF mRNA expression, the specificity and positive predictive value of Trx1 mRNA+RocF mRNA series connection in predicting ulcer+gastric cancer were the highest, and the misdiagnosis rate was the lowest; the sensitivity and negative predictive value of Trx1 mRNA+RocF mRNA parallel connection in predicting ulcer+gastric cancer were the highest, and the missed diagnosis rate was the lowest. Conclusion The combined detection of Trx1 mRNA and RocF mRNA can be used to screen highly pathogenic Hp and to predict the outcome of infection.