The Expression Significance Of LncRNA MEG3 And GDF-15 In Peripheral Blood Of Chronic Obstructive Pulmonary Disease

BackgroundChronic obstructive pulmonary disease(COPD)is the most common chronic airway inflammatory disease of the respiratory system.By 2020,it has become the third leading cause of death in the world,posing a great threat to human health.At present,the main clinical methods for the diagnosis and severity assessment of COPD are pulmonary function detection,clinical symptoms and subjective feelings of patients.However,the above indicators are greatly affected by the patient’s coordination ability and subjective factors.Therefore,it is particularly important to find objective biomarkers to accurately evaluate the severity and predict the prognosis of patients so as to guide individual clinical treatment.LncRNA MEG3 is a tumor suppressor gene that is extensively involved in a variety of pathophysiological processes such as cell proliferation,apoptosis,migration and angiogenesis.Previous studies have found that lncRNA MEG3 is not only significantly overexpressed in lung tissues of COPD patients,but also mediates apoptosis and inflammatory response of lung endothelial cells through gene chip technology.However,there are few studies on the assessment of the severity and prognosis of COPD.GDF-15 is a cytokine rapidly produced by macrophages after adverse stimulation,which can inhibit the proliferation of pulmonary endothelial cells and promote their apoptosis to participate in the occurrence of COPD.It has been reported that lncRNA MEG3 stimulates GDF-15 expression through p53 gene,so lncRNA MEG3 may affect the occurrence and development of chronic obstructive pulmonary disease through GDF-15.ObjectiveTo study the expression levels,correlation with clinical indexes and clinical significance of lncRNA MEG3 and GDF-15 in COPD patients.To explore its value in diagnosis,staging,disease evaluation and prognosis prediction of COPD patients.MethodsA total of 28 patients with acute exacerbation chronic obstructive pulmonary disease group(AE-COPD),15 patients with stable COPD and 26 healthy control group(HCs)were selected from the First Affiliated Hospital of Zhengzhou University from August to December 2020.Peripheral blood samples and clinical information were collected within 24 hours after admission,and the expression levels of lncRNA MEG3 were detected by real-time quantitative polymerase chain reaction(qPCR),and the expression levels of GDF-15 were detected by ELISA.All patients were followed up to December 2021.Analyzing the expression significance of lncRNA MEG3 and GDF-15 in peripheral blood of patients with COPD.Results1.The expressions of LncRNA MEG3 and GDF-15 were increased in COPD patients(P<0.05),and the increase was more significant in AE-COPD patients(P<0.05).Grading the indicators used to assess the severity of COPD patients,then the expression levels of LncRNA MEG3 and GDF-15 in patients with different grades were calculated respectively.It was found that GDF-15 and LncRNA MEG3 expression levels were higher in patients with CAT score≥20,mMRC grade≥2,hospitalization for acute exacerbation≥1times in the past year,and elevated CRP(P<0.05).The expression level of GDF-15 was higher in patients with elevated PCT(P<0.05).2.The expression levels of LncRNA MEG3 and GDF-15 in COPD patients were positively correlated with CAT score,mMRC grade and CRP(P<0.05),besides,GDF-15 was positively correlated with PCT(P<0.05).However,there was no significant correlation between LncRNA MEG3 expression level and GDF-15 in COPD patients(P>0.05).3.ROC curve was applied to analyze the diagnostic value of LncRNA MEG3 and GDF-15 for COPD and its stages.It was found that LncRNA MEG3,GDF-15 and LncRNA MEG3 combined with GDF-15 has certain diagnostic value for COPD.The optimal critical values were 0.80 and 40.76ng/mL,respectively.The Area under curve(AUC)were 0.661(95%CI 0.524-0.798),0.694(95%CI 0.568-0.819),0.754(95%CI 0.627-0.879),respectively.The sensitivity and specificity were 76.9%and 60%;48.8%and 87.5%;50%and 94.7%,respectively.LncRNA MEG3 combined with GDF-15.has certain diagnostic value for AE-COPD,with an AUC of 0.737(95%CI 0.580-0.893),sensitivity and specificity of 68%and 85.7%,respectively.4.Among 28 patients with AE-COPD,16 patients(88.9%)had adverse outcomes such as death or re-acute exacerbation within 1 year after discharge.The expression levels of LncRNA MEG3 and GDF-15 in patients with poor prognosis were higher than those without adverse prognosis(P<0.05).ROC curve analysis showed that LncRNA MEG3,GDF-15 and LncRNA MEG3 combined with GDF-15 could all be used to diagnose AE-COPD patients with poor prognosis,and the optimal cut off values were 1.53 and 51.34ng/ml,respectively.AUC were 0.813(95%CI 0.647-0.980),0.753(95%CI 0.563-0.944),0.947(95%CI 0.866-1.00),sensitivity and specificity were 60%and 100%;62.5%and 91.67%;86.7%and 90%,respectively.5.Logistic regression was further used to analyze the influencing factors of adverse events in COPD patients,and it was found that LncRNA MEG3,GDF-15,mMRC3-4 and≥1 time hospitalization with acute exacerbation in the last year were all risk factors for adverse events in COPD patients in univariate regression analysis.Multivariate Logistic regression analysis(stepwise regression based on conditional parameters)found that only≥1 time hospitalization with acute exacerbation in the last year was the risk factor for adverse events in COPD patients,with an odds ratio of 32.67,95%CI(2.852-374.135,P<0.05).Conclusion1.The higher the expression levels of LncRNA MEG3 and GDF-15 in peripheral blood,the more serious the disease of COPD patients is,and the expression levels of LncRNA MEG3 and GDF-15 provide certain reference value for the diagnosis,disease staging and severity assessment of COPD.2.LncRNA MEG3 and GDF-15 are highly expressed in COPD patients with adverse events,and can be used as new predictors of adverse events in COPD patients.Their combination has high diagnostic value.