Diagnostic Value And Mechanism Of Plasma MicroRNA-27 A/b In Patients With Acute Pulmonary Embolism

Background Pulmonary embolism(PE)is a group of diseases or clinical syndromes caused by various emboli blocking the pulmonary artery system.The common types of emboli are thromboembolism,gas embolism,fat embolism,amniotic fluid embolism,tumor cell embolism and so on.Among them,thromboembolism is the most common type of PE in clinical practice.Acute pulmonary embolism(APE)is the third most common cause of death from cardiovascular diseases after acute myocardial infarction and stroke.The attention of PE is increasing gradually at home and abroad,but the misdiagnosis and missed diagnosis rate is still high due to the unclear diagnosis.Currently,the diagnostic methods of APE include imaging examination and biomarkers.Because of imaging examination's high price,potential radiation and allergic reactions,it is limited for more application.D-dimer is a widely used biomarker in the diagnosis of APE.However,D-dimer has high sensitivity but low specificity,which is usually used to exclude PE.Therefore,there is an urgent need for new biomarkers to help diagnose PE accurately.Micro RNA(miRNA)is an endogenous non-coding single small RNA with 20-22 nucleotides,which regulates m RNA gene expression by inhibiting m RNA translation or promoting m RNA degradation.In recent years,miRNA has been found to play an important role in many cellular regulation processes,such as cell development,proliferation,differentiation and apoptosis.Many miRNAs expression patterns reflect a variety of pathophysiological processes and reveal the development of disease process.They are expected to be new biomarkers for various diseases.Mi R-27a/b are the two important component of the miR-27 gene family and have been shown to be abnormally expressed in cardiovascular diseases in recent years.Studies have shown that the tissue factor pathway inhibitor(TFPI)is closely related to the occurrence and development of thrombotic diseases.Other studies have shown that miR-27a/b can directly act on the 3'untranslated region(3'UTR)of TFPI,and overexpression of miR-27a/b leads to the abnormal expression of TFPI.The purpose of this study is to investigate the expression level of plasma miR-27a/b in APE patients and then evaluate their potential clinical significance.And the level of TFPI is further measured to evaluate the relationship between the expression of miR-27a/b and TFPI,and we discuss the possible mechanism of miR-27a/b in APE patients.Part? Expression level and diagnostic value of plasma microRNA-27a/b in patients with acute pulmonary embolismObjective To evaluate the expression of plasma miR-27a/b in patients with APE and determine the possibility of miR-27a/b as diagnostic biomarkers for APE.Method 102 APE patients were collected as experimental group,acute non ST elevation myocardial infarction(NSTEMI)(30 cases),pulmonary hypertension(PH)(30 cases),deep vein thrombosis(DVT)(30 cases)patients as non pulmonary embolism(non-APE)control group,and 100 healthy subjects were enrolled as healthy control group at the First Affiliated Hospital of Zhengzhou University.The levels of miR-27a/b and miR-16 were detected by quantitative real time polymerase chain reaction(q RT-PCR),and ACL TOP(Instrumentation Laboratory company)was used to detect D-dimer.Receiver operating characteristic(ROC)curves and the area under the ROC curves(AUC)were constructed to assess the sensitivity and specificity of miRNAs for distinguishing APE group from the control group and to assess the diagnostic accuracy,respectively.Result 1.The expression level of miR-27 a was significantly increased in APE patients compared with non-APE and healthy control groups(0.158 ± 0.044 vs.0.092 ± 0.038,P<0.001;0.158 ± 0.044 vs.0.037 ± 0.028,P<0.001);The expression level of miR-27 b also increased compared with non-APE and healthy control groups(0.099 ± 0.026 vs.0.054 ± 0.021,P<0.001;0.099 ± 0.026 vs.0.042 ± 0.013,P<0.001).2.The AUC of miR-27 a distinguishing APE patients from non-APE patients and healthy control were 0.776,0.882,respectively;The sensitivity were 83.3%,93.8%,respectively;The specificity were 70.8%,83.3%,respectively.3.The AUC of miR-27 b distinguishing APE patients from non-APE patients and healthy control were 0.731,0.795,respectively;The sensitivity were 85.4%,89.6%,respectively;The specificity were 71.3%,61.9%,respectively.4.The AUC of D-dimer distinguishing APE patients from non-APE patients and healthy control were 0.718,0.861,respectively;The sensitivity were 77.1%,100.0%,respectively;The specificity were 77.0%,61.5%,respectively.5.The AUC of miR-27 a combined with miR-27 b distinguishing APE patients from non-APE patients and healthy control were 0.876,0.859,respectively;The sensitivity were 72.8%,91.7%,respectively;The specificity were 88.2%,83.3%,respectively.The AUC of miR-27 a combined with D-dimer distinguishing APE patients from non-APE patients and healthy control were 0.899,0.928,respectively;The sensitivity were 87.5%,94.1%,respectively;The specificity were 83.3%,91.7%,respectively.The AUC of miR-27 b combined with D-dimer distinguishing APE patients from non-APE patients and healthy control were 0.828,0.885,respectively;The sensitivity were 75.0%,90.8%,respectively;The specificity were 88.5%,73.1%,respectively.The AUC of miR-27a/b combined with D-dimer distinguishing APE patients from non-APE patients and healthy control were 0.879,0.934,respectively;The sensitivity were 70.8%,89.6%,respectively;The specificity were 91.7%,92.5%,respectively.Conclusion Plasma miR-27a/b can effectively distinguish APE and non-APE,as well as healthy control with high sensitivity and specificity.Combining miR-27 a or miR-27 b with D-dimer can improve sensitivity and specificity to enhance the diagnostic value of APE.Our results showed that circulating miR-27 a and miR-27 b might be potential novel diagnostic biomarkers in APE patients.Part? Correlation between plasma microRNA-27a/b levels and tissue factor pathway inhibitor levels in patients with acute pulmonary embolismObjective To investigate the expression level of tissue factor pathway inhibitor(TFPI)in APE patients and the correlation between the plasma miR-27a/b and TFPI.Methods The level of plasma TFPI was detected by TFPI enzyme linked immunosorbent assay(ELISA)kit,and the correlation between plasma miR-27a/b and TFPI levels in APE patients was analyzed by Spearman correlation analysis.Results The plasma concentration of TFPI in APE patients was higher than healthy controls(44.25±6.16 ng/m L,20.05±3.49 ng/m L,respectively).The difference was statistically significant between the two groups(P<0.0001).There was a linear correlation between miR-27 a and TFPI(r = 0.632,P = 0.015).Similarly,there was also a linear correlation between miR-27 b and TFPI(r = 0.531,P = 0.005).Conclusion The level of TFPI is increased in APE patients,which is related to the expression level of miR-27a/b.The miR-27a/b may be involved in the occurrence and development of APE.The specific mechanism of miR-27a/b in APE needs to be further studied.