IRF1 as a potential biomarker in Mycobacterium tuberculosis infection

• Published in: Journal of cellular and molecular medicine Vol. 25; no. 15; pp. 7270 - 7279
• Main Authors: Wu, Liwei, Cheng, Qiliang, Wen, Zilu, Song, Yanzheng, Zhu, Yijun, Wang, Lin
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.08.2021; John Wiley and Sons Inc
• Subjects: biomarker; Biomarkers; Biomarkers - metabolism; Cell activation; Cell adhesion; Cell adhesion & migration; Cytokines; Cytokines - metabolism; differentially expressed gene (DEG); DNA microarrays; Folic acid; Gene expression; Gene Regulatory Networks; Genomes; Health care; HIV; Human immunodeficiency virus; Humans; Infections; Interferon regulatory factor 1; Interferon Regulatory Factor-1 - genetics; Interferon Regulatory Factor-1 - metabolism; network analysis; Online data bases; Open source software; Original; protein; protein interaction; Protein Interaction Maps; Proteins; Public health; Statistical analysis; Transcription activation; Transcriptome; Tuberculosis; tuberculosis (TB); Tuberculosis, Pulmonary - genetics; Tuberculosis, Pulmonary - metabolism; Tuberculosis, Pulmonary - pathology; Up-Regulation; South Africa; differentially expressed gene (DEG); network analysis; protein interaction; biomarker; tuberculosis (TB); protein
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.16756

Pulmonary tuberculosis (PTB) is a major global public health problem. The purpose of this study was to find biomarkers that can be used to diagnose tuberculosis. We used four NCBI GEO data sets to conduct analysis. Among the four data sets, GSE139825 is lung tissue microarray, and GSE83456, GSE19491 and GSE50834 are blood microarray. The differential genes of GSE139825 and GSE83456 were 68 and 226, and intersection genes were 11. Gene ontology (GO) analyses of 11 intersection genes revealed that the changes were mostly enriched in regulation of leucocyte cell‐cell adhesion and regulation of T‐cell activation. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEGs revealed that the host response in TB strongly involves cytokine‐cytokine receptor interactions and folate biosynthesis. In order to further narrow the range of biomarkers, we used protein‐protein interaction to establish a hub gene network of two data sets and a network of 11 candidate genes. Eventually, IRF1 was selected as a biomarker. As validation, IRF1 levels were shown to be up‐regulated in patients with TB relative to healthy controls in data sets GSE19491 and GSE50834. Additionally, IRF1 levels were measured in the new patient samples using ELISA. IRF1 was seen to be significantly up‐regulated in patients with TB compared with healthy controls with an AUC of 0.801. These results collectively indicate that IRF1 could serve as a new biomarker for the diagnosis of pulmonary tuberculosis.