Tuberculosis (TB) continues to pose significant challenges to global health, affecting approximately 7.5 million people annually and causing considerable mortality, particularly from drug-resistant strains. The urgency of effective therapeutic strategies has led researchers to explore novel biomarkers through advanced techniques such as transcriptomics.
A recent study published has identified four core genes associated with the progression of tuberculosis: Rac Family Small GTPase 1 (RAC1), Ring-Box 1 (RBX1), Mitochondrial Ribosomal Protein L33 (MRPL33), and ELAV Like RNA Binding Protein 1 (ELAVL1). This research highlights these genes' potential as biomarkers for tuberculosis severity and progression.
TB is caused by Mycobacterium tuberculosis (Mtb) and poses serious public health risks worldwide. The emergence of drug-resistant TB strains complicates medical responses and increases treatment difficulty. Therefore, new therapeutic targets and strategies are critically needed.
Transcriptomics—the analysis of RNA transcripts produced by the genome—offers insights by profiling gene expression changes over time. While most studies focus on specific time points, this research pioneers the longitudinal analysis of gene expression, discovering 1,228 genes with altered expression patterns associated with TB infection. The study utilized data from the Gene Expression Omnibus (GEO) database, ensuring comprehensive analysis through two-way ANOVA and additional bioinformatics methods.
Using Gene Ontology (GO) enrichment analysis, the study found these genes involved in fundamental cellular functions such as DNA translation, RNA processing, and transcriptional regulation. Notably, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis linked these genes to significant metabolic processes, including fatty acid degradation and cholesterol metabolism.
Through protein-protein interaction (PPI) analysis and Receiver Operating Characteristic (ROC) curve analysis, the researchers validated the key roles of RAC1, RBX1, MRPL33, and ELAVL1, all showing strong associations with TB progression. These genes were confirmed through qPCR experiments, demonstrating their upregulation during Mtb infection in THP-1 macrophage cells.
RAC1 is known for its role as a GTPase affecting cellular processes such as growth and migration. Prior studies indicate its involvement with mycobacterial entry and inflammatory response modification. Similarly, RBX1 acts as part of E3 ubiquitin ligase complexes, potentially modifying protein stability and immune responses. The expression of MRPL33, linked to mitochondrial function, suggests involvement in the immune response during TB, and ELAVL1 may contribute to anti-infective processes.
According to the study, the findings suggest significant potential for these core genes to serve as targets for developing effective anti-TB therapies. They could lead to advancements, particularly for patients suffering from drug-resistant forms of the disease. The study concluded, "These four genes may serve as core biomarkers for TB progression and can be utilized in the development of more effective anti-tuberculosis drugs and host therapy."
Future research directions include validating these findings with larger clinical samples and exploring the mechanistic roles of these genes within host-Mtb interactions. Exploring the therapeutic efficacy of targeting these biomarkers could revolutionize TB treatment and improve outcomes for the millions affected worldwide.