Unveiling the crucial genomic players in pulmonary tuberculosis-associated ferroptosis through bioinformatics scrutiny

Tuberculosis (TB) is a persistent infectious disease primarily impacting the lungs. Despite its global prevalence, conventional diagnostic methods suffer from prolonged detection times and low sensitivity, leading to diagnostic challenges and suboptimal patient outcomes. Ferroptosis, which is marked by an accumulation of iron-dependent lipid peroxides and subsequent lipid peroxidation, has emerged as a promising prognostic indicator of various maladies. This study aims to identify and pinpoint ferroptosis-related genes pertinent to pulmonary tuberculosis (PTB), offering potential molecular indicators for the early diagnosis, treatment, and prognosis of PTB. Employing bioinformatics analysis and transcriptome sequencing data of tuberculosis patients, this research screened for differentially expressed ferroptosis-related genes in tuberculosis sourced from FerrDb, with subsequent identification of key genes. Whole blood samples collected from 10 tuberculosis patients and 10 healthy volunteers were used for fluorescence-based real-time quantitative polymerase chain reaction (qRT-PCR) to validate the expression levels of identified genes, laying the groundwork for early tuberculosis diagnosis and clinical intervention. A total of 20 differentially expressed ferroptosis-related genes were identified from the database. Gene Ontology functional enrichment analysis highlighted their involvement in biological processes like hypoxia response, enzyme activity, and autophagy. By constructing a protein-protein interaction network via STRING and integrating it with enrichment analysis, key ferroptosis genes in PTB, including HRAS, ATF3, MAPK8, ATM, IDH1, and HIF1A, were singled out. The results of qRT-PCR demonstrate significantly elevated expression levels of ATF3 and MAPK8 in PTB patients compared to those of healthy controls (P < 0.05). ATF3 and MAPK8 emerged as pivotal ferroptosis-related genes in PTB, holding promise as molecular markers for PTB diagnosis and treatment.