Screening And Identification Of Potential Plasma Biomarkers For Pulmonary Tuberculosis Using LncRNAs Microarray

Background:Pulmonary tuberculosis?TB?is a chronic infection caused by Mycobacterium tuberculosis?MTB?.Accurate and early diagnosis of TB is still lacking,making it difficult to control the TB infection and the ineffective treatment of TB,thus leading to dr?g-resistant TB.Therefore,effective methods for early diagnosis are imperative for preventing TB.In the present study,we identified differentially expressed lncRNAs in the plasma of TB patients and evaluated the potential role of lncRNAs in the early diagnosis of TB.Methods:In this study,lncRNA microarray was used to screen differentially expressed lncRNAs and mRNAs in the plasma of 33 TB patients and 11 control subjects.GO and KEGG analyses were used to study the functions of differentially expressed mRNAs,and the CNC network was constructed to study the relationship between differentially expressed IncRNAs and mRNAs.The qPCR method was used to validate the expression levels of lncRNAs in 52 TB patients and 11 control subjects,and ROC curve was used to evaluate the potential role of these IncRNAs in clinical diagnosis of TB.The CeRNA network was constructed to explore the potential targets of IncRNAs.Results:A total of 511 differentially expressed IncRNAs?163 up-regulated,348 down-regulated?and 411 differentially expressed mRNAs?127 up-regulated,284 down-regulated?were detected between TB patients and healthy controls.The enriched GO terms associated with differentially expressed mRNAs in TB patients included positive regulation of alpha-beta T cell activation,cellular response to interferon-gamma?IFN-??,positive regulation of T cell activation,major histocompatibility?MHC?protein complex,and the mitogen-activated protein kinase?MAPK?cascade.The KEGG pathways associated with differentially expressed mRNAs in TB patients included MTB infection and Jak-STAT signaling pathways.The qPCR results showed that the expression levels of NR₀38221?fold change=3.79,P<0.01?,NR₀03142?fold change=1.69,P<0.05?,and ENST00000570366?fold change=3.04,P<0.05?were up-regulated,while the expression level of ENST00000422183?fold change=2.11,P<0.001?was down-regulated in TB patients compared with the healthy control subjects.The area under the curve?AUC?value of the combination of the four IncRNAs was 0.845?95%CI,0.742-0.949;P<0.001,sensitivity=79.2%,specificity=75%?.The CeRNA analysis showed that totally 85 mRNAs and 404 miRNAs were correlated with the four IncRNAs.Conclusions:?1?The differentially expressed lncRNAs were associated with the pathological process of TB;?2?GO,KEGG and CNC analyses showed that the abnormal expression of IncRNAs mainly affected the activation of T cell regulation,intracellular pathways and extracellular receptors to regulate the pathological process of TB;?3?The diagnostic model based on these IncRNAs had supplementary value for clinical diagnosis of TB;?4?This study provided potential role of IncRNAs in early diagnosis of TB,and also provided basis for the further research of IncRNAs in TB.