EARLY MIRNA BIOMARKERS OF PULMONARY TUBERCULOSIS AND THEIR CLINICAL DIAGNOSTIC SIGNIFICANCE

Abstract

Background: Pulmonary tuberculosis (TB) is the most prevalent type of respiratory infectious disease, and early diagnosis is of critical importance. miRNAs, as biological markers, have potential diagnostic value, but their role in clinical diagnosis has not been fully recognized. Methods: The gene expression data from the GSE139871 dataset, comprising healthy control and TB control groups, were downloaded from the GEO platform. Differentially expressed genes (DEGs) were identified and GO and KEGG pathway analyses were performed using the DAVID 6.8 online tool. GO and KEGG analyses were also conducted for the downregulated genes. Additionally, the STRING online platform was used to obtain PPI networks and Hub proteins, and KEGG pathways involving Hub proteins were identified. The TargetScan online tool was employed to predict miRNAs associated with Hub proteins. RT-qPCR was then used to analyze the expression levels of miRNAs in peripheral blood mononuclear cells (PBMCs) from patients to identify miRNA expression differences. Results: A total of 37 differentially expressed genes were identified between the healthy control and TB control groups in the GSE139871 dataset, including 16 upregulated and 21 downregulated genes. GO analysis of the downregulated genes revealed biological processes (BP) including antigen processing and presentation of exogenous peptide antigen via MHC class II, antigen processing and presentation of peptide antigen via MHC class II, peptide or polysaccharide antigen presentation via MHC class II, MHC class II protein complex assembly, peptide antigen assembly with MHC class II protein complex, antigen processing and presentation of exogenous peptide antigen, and others. Cellular components (CC) included MHC class II protein complex, MHC protein complex, integral component of the lumenal side of the endoplasmic reticulum membrane, lumenal side of the membrane, clathrin-coated endocytic vesicle membrane, and others. Molecular functions (MF) involved MHC class II protein complex binding, MHC protein complex binding, MHC class II receptor activity, peptide antigen binding, immune receptor activity, peptide binding, and others. KEGG pathway analysis identified pathways including asthma, allograft rejection, antigen processing and presentation, graft-versus-host disease, type I diabetes mellitus, intestinal immune network for IgA production, hematopoietic cell lineage, autoimmune thyroid disease, viral myocarditis, and inflammatory bowel disease. CD74 and HLA-DQB1 were identified as having strong protein-protein interactions, with HLA-DQB1 being involved in numerous KEGG pathways. hsa-miR-152-3p, hsa-miR-148a-3p, and hsa-miR-148b-3p were found to be associated with the downregulation of HLA-DQB1 expression, with hsa-miR-152-3p showing statistically significant expression levels in the PBMCs of pulmonary tuberculosis patients. Conclusion: hsa-miR-152-3p could serve as a key clinical marker for pulmonary tuberculosis detection.