溃疡性结肠炎患者血清miR-21、miR-155表达与艰难梭菌感染的相关性分析

Analysis of the correlation between the expression of miR-21, miR-155 and clostridium difficile infection in patients with ulcerative colitis

目的 探究溃疡性结肠炎(UC)患者血清微小RNA-21(miR-21)、miR-155表达水平与艰难梭菌感染(CDI)的相关性。方法 选取2021年2月—2022年8月清华大学第一附属医院收治的124例UC患者为研究对象,根据UC患者是否感染艰难梭菌分为非CDI组58例和合并CDI组66例,同时选取55例健康体检者为健康对照组。收集所有受试者临床资料;检测血红蛋白(Hb)、白蛋白(Alb)、白细胞计数(WBC)、中性粒细胞比率(NEUT)、C反应蛋白(CRP)、红细胞沉降率(ESR)等生化指标;实时荧光定量PCR法检测血清中miR-21、miR-155表达水平;Pearson法分析UC合并CDI患者血清miR-21、miR-155表达水平与生化指标的相关性,多因素Logistic回归分析影响UC合并CDI发生的因素,受试者工作特征曲线(ROC)评价血清miR-21、miR-155对UC患者合并CDI的诊断价值。结果 Hb、Alb水平比较,合并CDI组<非CDI组<健康对照组(F/P=55.339/<0.001、433.328/<0.001),NEUT、CRP水平比较,合并CDI组>非CDI组>健康对照组(F/P=64.375/<0.001、532.313/<0.001);合并CDI组WBC、ESR水平高于非CDI组和健康对照组(P<0.05)。血清miR-21、miR-155表达水平比较,合并CDI组>非CDI组>健康对照组(F/P=207.397/<0.001、339.643/<0.001)。UC合并CDI患者血清miR-21与miR-155表达水平呈正相关(r/P=0.449/<0.001),血清miR-21、miR-155与WBC、NEUT、CRP、ESR均呈正相关(miR-21:r/P=0.257/0.037、0.490/<0.001、0.405/0.001、0.287/0.020;miR-155:r/P=0.313/0.011、0.526/<0.001、0.492/<0.001、0.310/0.011),与Hb、Alb均呈负相关(miR-21:r/P=-0.451/<0.001、-0.417/<0.001;miR-155:r/P=-0.436/<0.001、-0.397/<0.001)。Hb高、Alb高是UC合并CDI发生的保护因素[OR(95%CI)=0.527(0.349~0.767)、0.624(0.440~0.885)],NEUT高、CRP高、miR-21高、miR-155高是UC合并CDI发生的危险因素[OR(95%CI)=2.042(1.207~3.455)、4.620(1.086~19.659)、3.457(1.625~7.352)、4.527(1.791~11.440)]。血清miR-21、miR-155及二者联合诊断UC合并CDI患者的曲线下面积(AUC)分别为0.915、0.878、0.950;二者联合诊断的AUC高于单项指标诊断(Z/P=2.565/0.010、3.338/0.001)。结论 UC合并CDI患者血清中miR-21、miR-155表达均升高,二者是UC合并CDI发生的危险因素,联合检测可用于诊断UC合并CDI的发生。

Objective To explore the correlation between the expression levels of serum microRNA-21(miR-21)and miR-155 in patients with ulcerative colitis(UC)and Clostridium difficile infection(CDI).Methods One hundred and twenty-four patients with UC admitted to the First Affiliated Hospital of Tsinghua University from February 2021 to August 2022 were selected as the study subjects.According to whether the UC patients were infected with Clostridium difficile,they were divided into non-CDI group(58 cases)and combined CDI group(66 cases).At the same time,55 healthy persons were selected as the healthy control group.Collect clinical data of all subjects;Hemoglobin(Hb),albumin(Alb),white blood cell count(WBC),neutrophil ratio(NEUT),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR)and other biochemical indicators were detected;The expression levels of miR-21 and miR-155 in serum were detected by real-time fluorescence quantitative PCR;Pearson's method was used to analyze the correlation between the expression levels of serum miR-21 and miR-155 and biochemical indicators in patients with UC complicated with CDI.Multifactor logistic regression analysis was used to analyze the factors affecting the occurrence of UC complicated with CDI.The diagnostic value of serum miR-21 and miR-155 in patients with UC complicated with CDI was evaluated by the working characteristic curve(ROC)of subjects.Results Comparison of Hb and Alb levels,combined CDI group<non-CDI group<healthy control group(F/P=55.339/<0.001,433.328/<0.001),and comparison of NEUT and CRP levels,combined CDI group>non-CDI group>healthy control group(F/P=64.375/<0.001,532.313/<0.001).The levels of WBC and CRP in CDI group were higher than those in non-CDI group and healthy control group(P<0.05).Compared with the expression level of miR-21 and miR-155 in serum,the expression level of combined CDI group>non-CDI group<healthy control group(F/P=207.397/<0.001,339.643/<0.001).In patients with UC complicated with CDI,serum miR-21 was positively correlated with the expression level of miR-155(r/P=0.449/<0.001),and serum miR-21 and miR-155 were positively correlated with WBC,NEUT,CRP and ESR(miR-21:r/P=0.257/0.037,0.490/<0.001,0.405/0.001,0.287/0.020;miR-155:r/P=0.313/0.011,0.526/<0.001,0.492/<0.001,0.310/0.011)Alb was negatively correlated(miR-21:r/P=-0.451/<0.001,-0.417/<0.001.miR-155:r/P=-0.436/<0.001,-0.397/<0.001).High Hb and high Alb are protective factors for UC combined with CDI[OR(95%CI)=0.527(0.349-0.767),0.624(0.440-0.885)],and high NEUT,CRP,miR-21 and miR-155 are risk factors for UC combined with CDI[OR(95%CI)=2.042(1.207-3.455),4.620(1.086-19.659),3.457(1.625-7.352),4.527(1.791-11.440)].The area under curve(AUC)of serum miR-21,miR-155 and their combined diagnosis of UC with CDI were 0.915,0.878 and 0.950,respectively;The AUC of the combined diagnosis was higher than that of the single index diagnosis(Z/P=2.565/0.010,3.338/0.001).Conclusion The expression of miR-21 and miR-155 in the serum of patients with UC complicated with CDI are both increased,which are risk factors for the occurrence of UC complicated with CDI.Combined detection can be used to diagnose the occurrence of UC complicated with CDI.