Identification of ferroptosis-related key genes in tuberculosis by bioinformatics methods.

Abstract

Tuberculosis, induced by Mycobacterium tuberculosis (Mtb), continues to pose a significant global public health challenge. Ferroptosis has emerged as a pivotal factor in tuberculosis pathogenesis, however, the mechanism has not yet been fully clarified. Therefore, the aim of this study was to hypothesize and validate potential ferroptosis-related genes in Mtb infection through bioinformatics analysis, thereby offering insights for further investigation. The mRNA microarray expression profile datasets were sourced from the Gene Expression Omnibus. The differentially expressed genes (DEGs) were derived using GEO2R. Subsequently, the shared DEGs between the GSE174566 and GSE227851 datasets were intersected with the genes in the ferroptosis database. The ferroptosis-associated shared DEGs (Ferr-sDEGs) were validated in the GSE20050 dataset. They were subjected to PPI, Cytoscape and Friends analysis, the infiltration correlation of immune cells and qRT-PCR. A total of 11 Ferr-sDEGs were identified, and 9 genes were validated. These analyses revealed that the key Ferr-sDEGs contributed to ferroptosis during Mtb infection and these key Ferr-sDEGs were relatively independent, implying that ferroptosis may be triggered by various mechanisms. Concurrently, the infiltration and correlation analysis demonstrated that multiple types of immune cells could be activated by the key Ferr-sDEGs. Ultimately, qRT-PCR validated that the expression levels of key Ferr-sDEGs. In conclusion, ferroptosis serves a pivotal function in the pathogenesis of tuberculosis. IL1B, PTGS2, TNFAIP3, HMOX1, SOCS1, CD82, and NUPR1 may be vital genes associated with the ferroptosis induced by Mtb infection.