Circulating miR-26b-5p as a Potential Host-Derived Biomarker for Active Pulmonary Tuberculosis

Tuberculosis (TB) remains a major global infectious disease, and novel host-derived biomarkers are needed to improve diagnosis. Circulating microRNAs (miRNAs) are promising biomarkers due to their stability and immune regulatory functions; however, clinically validated TB-associated miRNAs remain limited. This study aimed to identify circulating miRNAs associated with active pulmonary TB.

This study included 90 participants: active pulmonary TB (n=30), cured TB (n=30), and healthy controls (n=30). Candidate miRNAs were screened by pooled plasma miRNA profiling and further examined using three publicly available miRNA datasets. Circulating miR-26b-5p was quantified by RT-qPCR. Associations with active TB status were assessed using logistic regression, and discriminatory performance was evaluated by ROC analysis. Putative miR-26b-5p target genes and enriched pathways were explored using bioinformatic analyses.

Microarray screening identified 108 candidate miRNAs, and cross-dataset analysis identified miR-26b-5p as the only overlapping candidate with consistent downregulation. Circulating miR-26b-5p was lower in active TB and higher in the clinically cured group. It remained associated with active-TB status after adjustment for BMI and PLR. miR-26b-5p showed an AUC of 0.867, while the combined model achieved an AUC of 0.956. Bioinformatic analysis identified 74 putative genes, with EP300, GSK3B, and PTEN as network hubs and PI3K-Akt among the enriched pathways.

Circulating miR-26b-5p was associated with active pulmonary TB and showed preliminary discriminatory value, supporting its further evaluation as a candidate host-response marker.