急性冠脉综合征患者外周血KLF2、CD62L、CCR7水平与病情及预后的关系

Relationship between peripheral blood KLF2,CD62L,and CCR7 levels and disease condition and prognosis in patients with acute coronary syndrome

目的观察急性冠脉综合征(ACS)患者外周血Kruppel样转录因子2(KLF2)、L-选择素(CD62L)、趋化因子受体7(CCR7)的表达水平,并探讨其与病情和预后的关系。方法前瞻性选取西安凤城医院2017年2月至2022年2月收治的214例ACS患者,根据类型不同分为不稳定型心绞痛(UA组)86例,ST段抬高型心肌梗死(STEMI组)75例,非ST段抬高型心肌梗死(NSTEMI组)53例,另选取同期100例健康体检者作为对照组。比较各组受检者及不同Killip心功能分级患者外周血KLF2 mRNA、CD62L、CCR7 mRNA的表达水平,并采用Pearson相关分析法分析KLF2 mRNA、CD62L、CCR7 mRNA与Gensini评分的关系。随访1年,统计患者主要不良心血管事件(MACE)发生率,根据有无MACE发生分为预后良好组和预后不良组;采用多因素Logistic回归分析探究ACS预后影响因素,应用受检者工作特征曲线(ROC)分析外周血KLF2 mRNA、CD62L、CCR7 mRNA对ACS预后的预测价值。结果各组受检者对比发现,KLF2 mRNA、CD62L表达水平为STEMI组<NSTEMI组<UA组<对照组,CCR7 mRNA为STEMI组>NSTEMI组>UA组>对照组,差异均有统计学意义(P<0.05);不同心功能分级患者对比发现,KLF2 mRNA、CD62L表达水平为Ⅳ级<Ⅲ级<Ⅱ级<Ⅰ级,CCR7 mRNA为Ⅳ级>Ⅲ级>Ⅱ级>Ⅰ级,差异均有统计学意义(P<0.05);经Pearson相关分析法分析结果显示,外周血KLF2 mRNA、CD62L表达与Gensini积分均呈负相关(P<0.05),CCR7 mRNA表达与Gensini积分呈正相关(P<0.05);随访1年内,16例失访,198例有效随访患者中58例预后不良,140例预后良好。预后不良组患者的外周血KLF2 mRNA、CD62L表达水平分别为0.31±0.12、(45.30±10.85)%,明显低于预后良好组的0.54±0.15、(60.49±14.12)%,CCR7 mRNA表达水平为3.01±0.48,明显高于预后良好组的1.84±0.43,差异均有统计学意义(P<0.05);经多因素Logistic回归分析结果显示,合并高血压、合并糖尿病、吸烟史、CCR7 mRNA高表达、Gensini积分是ACS患者预后不良的危险因素(P<0.05),KLF2 mRNA高表达、CD62L高表达是其保护因素(P<0.05);经ROC分析结果显示,外周血KLF2 mRNA、CD62L、CCR7 mRNA及三者联合预测ACS患者预后不良的曲线下面积(AUC)分别为0.899、0.808、0.964、0.994。结论ACS患者外周血KLF2、CD62L表达下调,CCR7表达升高,且与患者心功能分级及冠脉病变程度有关,三者联合检测对ACS预后有较高预测价值。

Objective To observe the expression levels of Kruppel-like factor 2(KLF2),L-selectin(CD62L),and chemokine receptor 7(CCR7)in peripheral blood of patients with acute coronary syndrome(ACS)and explore their relationship with disease condition and prognosis.Methods A total of 214 patients with ACS who were treated in Xi'an Fengcheng Hospital from February 2017 to February 2022 were prospectively selected and divided into unstable angina group(UA group,86 cases),ST-segment elevation myocardial infarction group(STEMI group,75 cases),and non-ST-segment elevation myocardial infarction group(NSTEMI group,53 cases)according to different types.Another 100 subjects undergoing physical examination during the same period were enrolled as control group.The expression levels of KLF2 mRNA,CD62L,and CCR7 mRNA in peripheral blood were compared among the four groups and among patients with different Killip cardiac function grades.The relationship of KLF2 mRNA,CD62L,and CCR7 mRNA with Gensini score was analyzed by Pearson correlation analysis.After 1 year of follow-up,the incidence rate of major adverse cardiovascular events(MACE)was statistically analyzed.The patients were classified into good prognosis group and poor prognosis group according to the presence or absence of MACE.Multivariate Logistic regression analysis was used to explore the influencing factors of prognosis of ACS,and receiver operating characteristic(ROC)curve was applied to analyze the predictive value of peripheral blood KLF2 mRNA,CD62L,and CCR7 mRNA on prognosis of ACS.Results Expression levels of KLF2 mRNA and CD62L were increased successively in STEMI group,NSTEMI group,UA group,and control group,while CCR7 mRNA was decreased successively in STEMI group,NSTEMI group,UA group,control group,with statistically significant differences(P<0.05).Comparison on the expression levels of KLF2 mRNA and CD62L among patients with different cardiac function grades were manifested as gradeⅣ<gradeⅢ<gradeⅡ<gradeⅠ,while CCR7 mRNA was shown as gradeⅣ>gradeⅢ>gradeⅡ>gradeⅠ(P<0.05).Pearson correlation analysis results showed that the expressions of KLF2 mRNA and CD62L in peripheral blood were negatively correlated with Gensini score(P<0.05),and the expression of CCR7 mRNA was positively correlated with Gensini score(P<0.05).Within 1 year of follow-up,16 cases were lost to follow-up,and there were 58 cases of poor prognosis and 140 cases of good prognosis among the 198 successfully followed-up patients.The expression levels of peripheral blood KLF2 mRNA and CD62L were 0.31±0.12 and(45.30±10.85)%in poor prognosis group,significantly lower than 0.54±0.15 and(60.49±14.12)%in good prognosis group,while the expression of CCR7 mRNA was 3.01±0.48,significantly higher than 1.84±0.43 in good prognosis group,with statistically significant differences(P<0.05).Multivariate Logistic regression analysis showed that hypertension,diabetes mellitus,smoking history,high expression of CCR7 mRNA,and Gensini score were risk factors of poor prognosis in patients with ACS(P<0.05),and high expression of KLF2 mRNA and high expression of CD62L were protective factors(P<0.05).ROC analysis results revealed that the areas under ROC curves(AUCs)of peripheral blood KLF2 mRNA,CD62L,CCR7 mRNA,and their combination on predicting poor prognosis in patients with ACS were 0.899,0.808,0.964,and 0.994,respectively.Conclusion The expression levels of KLF2 and CD62L in peripheral blood of patients with ACS are down-regulated,while the expression of CCR7 is increased.The above three indicators are related to the grading of cardiac function and the degree of coronary artery lesion.Combined detection of the three indicators has high predictive value on the prognosis of ACS.