急性胰腺炎患者血浆miR-21-3p和miR-551-5p表达水平及临床意义

Expression and clinical significance of microRNA-21-3p and microRNA-551-5p in patients with acute pancreatitis

目的探讨血浆微小RNA-21-3p(miR-21-3p)和miR-551-5p表达水平对急性胰腺炎(AP)的诊断及预后预测的价值。方法采用前瞻性观察性研究,选择2017年1月1日至2019年12月31日海南省第三人民医院收治的AP患者作为研究对象。根据病情严重程度将患者分为轻症急性胰腺炎(MAP)组、中度重症急性胰腺炎(MSAP)组和重症急性胰腺炎(SAP)组,均于入院次日采集空腹静脉血,采用实时定量聚合酶链反应(PCR)检测血浆miR-21-3p及miR-551-5p表达水平。以患者康复出院或死亡作为研究终点。另外以同期50例健康体检者作为健康对照组。用受试者工作特征曲线(ROC)分析血浆miR-21-3p和miR-551-5p表达水平对SAP诊断及预后评估的价值。采用Pearson法分析SAP患者血浆miR-21-3p与miR-551-5p表达水平的相关性。结果共入选164例AP患者,其中MAP 72例,MSAP 47例,SAP 45例。SAP患者中存活27例,死亡18例;MAP组和MSAP组无死亡病例。AP患者血浆miR-21-3p、miR-551-5p表达水平均明显高于健康对照组〔miR-21-3p(2-ΔΔCt):2.17±0.90比0.65±0.12,miR-551-5p(2-ΔΔCt):1.80±0.73比0.42±0.08,均P<0.01〕;且随病情程度加重,患者血浆miR-21-3p、miR-551-5p表达水平逐渐升高(F值分别为11.635、10.204,均P<0.01),SAP组血浆miR-21-3p、miR-551-5p表达水平明显高于MSAP组和MAP组〔miR-21-3p(2-ΔΔCt):3.16±1.08比1.85±0.71、1.70±0.64,miR-551-5p(2-ΔΔCt):2.63±0.95比1.52±0.46、1.36±0.40,均P<0.01〕。ROC曲线分析显示,miR-21-3p与miR-551-5p联合诊断SAP的ROC曲线下面积(AUC)和95%可信区间(95%CI)明显高于miR-21-3p或miR-551-5p单项指标〔0.898(0.841~0.960)比0.820(0.763~0.882)、0.806(0.748~0.867),Z1=4.480、Z2=4.916,均P<0.05〕,其敏感度为90.7%,特异度为85.0%。SAP死亡组患者血浆miR-21-3p、miR-551-5p表达水平均明显高于存活组〔miR-21-3p(2-ΔΔCt):3.75±1.17比2.66±0.87,miR-551-5p(2-ΔΔCt):3.17±1.04比2.24±0.83,均P<0.01〕。ROC曲线分析显示,miR-21-3p与miR-551-5p联合预测SAP患者死亡的AUC和95%CI明显高于miR-21-3p或miR-551-5p单项指标〔0.933(0.875~0.996)比0.856(0.794~0.917)、0.816(0.759~0.874),Z1=4.395、Z2=5.520,均P<0.05〕,其敏感度为95.2%,特异度为87.5%。相关性分析显示,SAP患者血浆miR-21-3p与miR-551-5p表达水平呈显著正相关(r=0.827,P<0.001)。结论血浆miR-21-3p和miR-551-5p表达水平升高与AP患者病情严重程度呈正相关,二者联合检测对SAP诊断和预后评估具有较好的价值。

Objective To investigate the diagnostic and diagnostic values of plasma microRNA-21-3p(miR-21-3p)and miR-551-5p expression in patients with acute pancreatitis(AP).Methods A prospective observational study was conducted.AP patients admitted to the Third People's Hospital of Hainan Province from January 1st 2017 to December 31st 2019 were enrolled.The patients were divided into mild acute pancreatitis(MAP)group,moderate severe acute pancreatitis(MSAP)group and severe acute pancreatitis(SAP)group according to their severity.Fasting venous blood was collected from all subjects the day after admission,and real-time quantitative polymerase chain reaction(PCR)as used to detect the expression levels of plasma miR-21-3p and miR-551-5p.Rehabilitation,discharge or death were end points of study.In addition,50 healthy people in the same period were selected as the control group.The receiver operating characteristic(ROC)curve was used to analyze the value of the expression levels of plasma miR-21-3p and miR-551-5p for the diagnosis and prognosis of SAP.Pearson correlation was used to analyze the relationship between the expressions of miR-21-3p and miR-551-5p in SAP patients.Results A total of 164 AP patients were enrolled,including 72 MAP patients,47 MSAP patients and 45 SAP patients.Among the SAP patients,27 cases survived and 18 cases died.There were no deaths in MAP group and MSAP group.The levels of plasma miR-21-3p and miR-551-5p in AP group were significantly higher than those in control group[miR-21-3p(2-ΔΔCt):2.17±0.90 vs.0.65±0.12,miR-551-5p(2-ΔΔCt):1.80±0.73 vs.0.42±0.08,both P<0.01].The expression levels of plasma miR-21-3p and miR-551-5p in AP patients increased gradually with the aggravation of the disease(F values were 11.635,10.204 respectively,both P<0.01),and the expression levels of plasma miR-21-3p and miR-551-5p in SAP group were significantly higher than those in MSAP group and MAP group[miR-21-3p(2-ΔΔCt):3.16±1.08 vs.1.85±0.71,1.70±0.64;miR-551-5p(2-ΔΔCt):2.63±0.95 vs.1.52±0.46,1.36±0.40;all P<0.01].ROC curve analysis showed that the area under the ROC curve(AUC)and 95%confidence interval(95%CI)of the joint diagnosis of SAP with miR-21-3p and miR-551-5p were significantly higher than that of miR-21-3p or miR-551-5p alone[0.898(0.841-0.960)vs.0.820(0.763-0.882),0.806(0.748-0.867),Z1=4.480,Z2=4.916,both P<0.05],and the sensitivity was 90.7%and the specificity was 85.0%.The expression levels of plasma miR-21-3p and miR-551-5p in the death group of SAP patients were significantly higher than those in the survival group[miR-21-3p(2-ΔΔCt):3.75±1.17 vs.2.66±0.87,miR-551-5p(2-ΔΔCt):3.17±1.04 vs.2.24±0.83,both P<0.01].ROC curve analysis showed that the AUC and 95%CI of the combined prediction of death in SAP patients with miR-21-3p and miR-551-5p were significantly higher than that of miR-21-3p or miR-551-5p alone[0.933(0.875-0.996)vs.0.856(0.794-0.917),0.816(0.759-0.874),Z1=4.395,Z2=5.520,both P<0.05],and the sensitivity was 95.2%and the specificity was 87.5%.Correlation analysis showed a positive correlation between the expression level of plasma miR-21-3p and miR-551-5p in SAP patients(r=0.827,P<0.001).Conclusions The increased expression of plasma miR-21-3p and miR-551-5p are positively correlated with the severity of AP patients.The combination of the two items has a better value in the diagnosis and prognosis evaluation of SAP.