The Diagnostic Value Of MicroRNA In Different Mycobacterium Tuberculosis Infection States

Objective: Tuberculosis(TB)is an infectious disease caused by Mycobacterium tuberculosis(MTB).At present,its incidence rate has partially recovered,and the global burden of TB is still heavy.Existing methods for diagnosing TB have some limitations,and the diagnosis of TB remains challenging.Circulating micro RNA(miRNA)has been proven to play an important role in the pathogenesis of TB.More and more studies have shown that circulating miRNA can be used as a potential biomarker of TB.The purpose of this study is to summarize and analyze the research of circulating miRNAs in the diagnosis of active tuberculosis(ATB),explore the diagnostic performance of different miRNAs in ATB,and evaluate the ideal miRNA for the diagnosis of ATB.Methods: Studies evaluating the role of miRNA in the diagnosis of active tuberculosis through computerized searches of the databases Pub Med,Embase,Web of science,and Cochrane library built up to May 15,2022.The studies were screened strictly according to inclusion and exclusion criteria,and data from the included studies were extracted and then statistically analyzed.The quality of the included studies was completed by the Quality Assessment of Diagnostic Accuracy Studies-2(QUADAS-2)scale.The pooled sensitivity,specificity,positive likelihood ratio(PLR),negative likelihood ratio(NLR)and diagnostic ratio(DOR)were calculated for each miRNA using meta-disc software.The area under the summary receiver operating characteristic curve was used to summarize the overall diagnostic performance of each miRNA.By subgroup analysis,factors that may affect the diagnostic performance of miRNA,such as TB burden,age of subjects,specimen source and miRNA dysregulation type,were analyzed.Finally,the Deeks funnel plot was used to examine the publication bias of the study.Results: A total of 16 studies involving 1964 subjects were included,including 974 patients with active TB and 990 healthy controls.We evaluated the overall sensitivity,specificity,PLR,NLR and DOR of six miRNAs,including miR-31,miR-144,miR-125 b,miR-155,miR-29 a and miR-146 a,and plotted summary receiver operating characteristic(SROC)curves then calculated the area under the curve(AUC).All of the six miRNAs had good diagnostic performance(AUC>0.7),among which the highest AUC of miR-31 was 0.9857,the highest sensitivity of miR-31 was 0.97,and the highest specificity of miR-144 was 0.94.Subgroup analysis of miR-29 a,miR-146 a,miR-125 b,and miR-155 was conducted based on TB burden,age of subjects,specimen source and miRNA dysregulation type.The results of subgroup analysis showed that the above factors could affect the diagnostic performance of miRNA.Conclusion: The meta-analysis showed that miR-31,miR-144,miR-125 b,miR-155,miR-29 a and miR-146 a could be used as promising biomarkers of active tuberculosis.TB burden,age of subjects,specimen source and miRNA dysregulation type affect the diagnostic performance of miRNA.Objective: Latent tuberculosis(LTBI)is a condition in which the host is infected with Mycobacterium tuberculosis and has not yet developed disease,but there is a risk of developing into active tuberculosis(ATB).At present,there is no "gold standard" diagnostic method for LTBI.The purpose of this study was to evaluate the value of six miRNAs,miR-31,miR-144,miR-125 b,miR-155,miR-29 a and miR-146 a,in identifying active and latent tuberculosis.Methods: The data set describing the expression of miRNA in active and latent tuberculosis was searched in the GEO database by terms.The expression data of miR-31,miR-144,miR-125 b,miR-155,miR-29 a and miR-146 a in two groups of patients were extracted in GSE29190 dataset.The ability to distinguish ATB and LTBI was estimated by analyzing the differentially expressed miRNA and validated them in the GSE149645 dataset.Results: The expression of miR-146 a was significantly different in the two different disease states of Mycobacterium tuberculosis infection.miR-146 a had good ability to distinguish ATB and LTBI.Conclusion: miR-146 a is promising biomarkers for distinguishing active and latent tuberculosis.Objective: In the previous meta-analysis,we found that miR-31,miR-144,miR-125 b,miR-155,miR-29 a and miR-146 a have good performance in diagnosing active tuberculosis(ATB).In this part of the study,we verified the diagnostic performance of these six miRNAs through experiments.Methods: 20 patients diagnosed with ATB in March 2023 were selected as the ATB group,and 20 healthy patients who underwent physical examination in hospital during the same period were selected as the healthy control group.The expression levels of miR-31,miR-144,miR-125 b,miR-155,miR-29 a and miR-146 a were detected by real-time fluorescence quantitative PCR.The expression levels of six miRNAs in the blood of patients in the two groups were observed,and the differentially expressed miRNAs were analyzed to evaluate their ability as diagnostic markers of ATB.Results: There were differences between miR-29 a,miR-125 b,miR-146 a and miR-155 in the two groups of patients,among which,miR-29 a,miR-146 a and miR-155 had a good ability to distinguish between patients with ATB and healthy people.Conclusion: miR-29 a,miR-146 a and miR-155 these three miRNAs can serve as potential biomarkers of ATB.