B99-04 A Ptpro-related Five Gene Signature Differentiates Tuberculosis

Abstract Background Tuberculosis (TB), infected by Mycobacterium tuberculosis (MTB), remains a significant global health challenge, exacerbated by rising drug resistance and the shortcomings of current diagnostic methods. Macrophages, key players in the innate immune response to TB, are regulated by the protein tyrosine phosphatase receptor type O (PTPRO), which influences their motility and immune activity. This study describes a PTPRO-associated gene signature is engineered and validated as a potential biomarker for TB diagnosis and therapeutic monitoring. Methods Using the TCGA lung cancer dataset, we identified PTPRO-associated differentially expressed genes by stratifying samples into high and low PTPRO expression groups. Subsequent analysis was performed on whole-blood transcriptomic data derived from the GEO database, including 16 TB patients, 8 pneumonia patients, 8 lung cancer patients, and 38 control subjects without disease. Intersecting these datasets, we identified a PTPRO-related five-gene (PO5) signature. TB risk scores were calculated for each individual based on PO5 gene expression, and diagnostic performance was assessed by receiver operating characteristic (ROC) analysis across validation cohorts The impact of anti-TB treatment on risk scores was also assessed. RT-qPCR was used to validate gene expression changes in MTB H37Ra-infected macrophages and in clinical blood samples. Results The PO5 gene signature, comprised of VAMP5, CD74, HLA-DPB1, RARRES3, and TGM2, was identified and validated in both MTB-infected THP1 macrophages and a newly recruited clinical TB cohort. TB risk scores based on PO5 gene signature effectively distinguished TB from healthy controls (AUC: 0.725-0.871), latent TB (AUC: 0.647-0.798), lung cancer (AUC: 0.658-1.000), and pneumonia (AUC: 0.712-1.000) across multiple validation datasets. Notably, TB scores decreased in response to anti-TB therapy, demonstrating potential for treatment monitoring. The diagnostic and prognostic utility of the PO5 gene signature was further validated in independent clinical cohorts. Conclusion The PO5 gene signature represents a promising independent blood-based biomarker panel for TB diagnosis and treatment monitoring, offering an effective alternative to conventional sputum-based diagnostics. This abstract is funded by: he Natural Science Foundation of Anhui Province (Grant No. 2408085MH234)