Whole transcriptome sequencing identifies key characteristics and potential therapeutic efficacy biomarkers CD1B, CD247, and CCNB1 in cured tuberculosis patients.

BACKGROUND: The extended therapeutic duration required for pulmonary tuberculosis (PTB) treatment and current limitations in bacteriological gold standards for cure assessment may lead to premature discharge of incompletely cured patients, thereby elevating risks of disease transmission and drug resistance emergence. Host-directed biomarker research holds promise as a valuable adjunct to existing PTB cure evaluation standards, potentially enhancing diagnostic precision and therapeutic monitoring. Transcriptomic biomarkers represent a promising research direction and constitute the focal point of this study.

METHODS: This study stratified participants into four groups: healthy controls (HC), PTB patients (TB0), 2-month PTB treatment patients (TB2), and cured PTB cases (TB6). Whole-transcriptome sequencing was systematically applied to peripheral blood mononuclear cells (PBMCs) to simultaneously profile mRNA, lncRNA, circRNA, and miRNA expression patterns, thereby constructing transcriptomic profiles characterizing PTB progression from disease to clinical resolution. Subsequently, the most significantly differentially expressed RNAs were prioritized as candidate biomarkers for therapeutic efficacy evaluation in PTB management.

RESULTS: Comparative analysis between TB0 and TB6 groups revealed an intricate interaction network comprising 26 differentially expressed mRNAs, 19 lncRNAs, 1 circRNA, and 2 miRNAs. Three mRNAs (CD1B, CD247, and CCNB1) demonstrating significant differential expression between TB0 and TB6 groups were systematically identified. These biomarkers collectively captured two critical biological hallmarks of successful PTB treatment: CD1B and CD247 signatures reflected the establishment of T-cell-mediated host immunity, while CCNB1 downregulation indicated mitigation of cell cycle-associated pathological damage. Notably, the lncRNA FMNL2 emerged as a potential cell cycle regulator, potentially mediating its effects through targeted interaction with CCNB1.

CONCLUSION: This investigation elucidates two pivotal biological signatures associated with PTB resolution, providing novel insights into the pathological mechanisms underlying treatment success. These molecular candidates not only show significant potential as biomarkers for therapeutic efficacy monitoring but may also serve as promising therapeutic targets for PTB intervention strategies.