m6A甲基转移酶样蛋白3在溃疡性结肠炎病人结肠组织中的表达及意义

Expression of N6-methyladenosine methyltransferase like 3 in colon tissue of patients with ulcerative colitis and its significance

目的:探讨m6A甲基转移酶样蛋白3(METTL3)在溃疡性结肠炎(UC)病人结肠组织中的表达及其临床意义。方法:纳入UC病人100例作为研究对象,依据Mayo评分方法判定病情活动度:轻度活动期30例,中度活动期34例,重度活动期36例。根据预后情况分为不良预后组(56例)和预后良好组(44例)。另以同期结肠息肉病人60例为对照组。通过qRT-PCR法检测UC病人及对照组结肠黏膜METTL3 mRNA的表达,采用免疫组织化学法检测UC病人METTL3蛋白水平。比较UC不同严重程度病人METTL3 mRNA及蛋白表达变化,分析其与UC严重程度及预后的关系;受试者工作特征(ROC)曲线评价METTL3 mRNA对UC预后的预测效能;Cox回归分析影响UC预后不良的相关因素。结果:研究组病人结肠黏膜METTL3 mRNA水平高于对照组,差异有统计学意义(P<0.01)。与轻度活动期相比较,中度活动期与重度活动期病人结肠黏膜METTL3 mRNA水平以及阳性率显著升高(P<0.05);与中度活动期相比较,重度活动期病人结肠黏膜METTL3 mRNA水平以及阳性率显著升高(P<0.05)。预后不良组病人Mayo评分、METTL3 mRNA水平、METTL3阳性表达率及CRP均显著高于预后良好组(P<0.05~P<0.01)。Spearman相关性分析结果显示,研究组病人METTL3 mRNA与Mayo评分呈正相关关系(r=0.540,P<0.05)。ROC结果显示,METTL3 mRNA诊断病人预后的曲线下面积为0.882(95%CI:0.813~0.951),灵敏度为82.10%,特异度为86.40%。Cox回归分析显示,Mayo评分、METTL3 mRNA水平升高是UC病人发生不良预后的独立危险因素(P<0.05)。结论:UC病人METTL3水平与预后有关,其高水平可提示病人预后不良。

Objective:To investigate the expression levels of N6-methyladenosine methyltransferase like 3(METTL3)in colon tissue of patients with ulcerative colitis(UC),and its clinical significance.Methods:A total of 100 UC patients were selected as the study subjects.The disease activity was determined by Mayo score method:30 cases were mildly active,34 cases were moderately active,and 36 cases were severely active.According to the prognosis,the patients were divided into the poor prognosis group(56 cases)and good prognosis group(44 cases).Another 60 patients with colonic polyp during the same period were selected as the control group.The expression levels of METTL3 mRNA in colonic ucosa of UC patients and control group were detected by qRT-PCR,and the level of METTL3 protein in UC patients was detected by immunohistochemistry.The mRNA and protein expression levels of METTL3 in patients with different UC severity were compared to analyze its relationship with the severity and prognosis of UC.The predictive efficacy of METTL3 mRNA in UC was evaluated by receiver operating characteristic(ROC)curve.Cox regression analysis was performed to analyze the related factors affecting the poor prognosis of UC.Results:The mRNA level of METTL3 in colonic mucosa of the study group was higher than that of control group,and the difference was statistically significant(P<0.01).Compared with the mildly active period,the METL3 mRNA level and positive rate of colonic mucosa in the moderately active period and severely active period were significantly higher(P<0.05).Compared with the moderately active period,the METL3 mRNA level and positive rate of colonic mucosa in the severely active period were significantly higher(P<0.05).The Mayo score,METL3 mRNA level,positive expression rate of METL3 and CRP in the poor prognosis group were significantly higher than those in good prognosis group(P<0.05 to P<0.01).The results of Spearman correlation analysis showed that there was a positive correlation between METTL3 mRNA and Mayo score in the study group(r=0.540,P<0.05).The results of ROC curve showed that the area under the curve of patients diagnosed with METTL3 mRNA was 0.882(95%CI:0.813-0.951),the sensitivity was 82.10%,and the specificity was 86.40%.The results of Cox regression analysis showed that Mayo score and METL3 mRNA levels were the independent risk factors of poor prognosis in UC patients(P<0.05).Conclusions:The METL3 level of UC patients is related to the prognosis,and its high level may indicate a poor prognosis.