Exploring biomarkers related to exosome in primary immune thrombocytopenia based on transcriptomics and experimental verification

Background Primary Immune Thrombocytopenia (ITP) is an autoimmune disease with thrombocytopenia and bleeding tendency. Exosomes mediate abnormal crosstalk between immune cells and megakaryocytes in ITP, making exosome-related biomarkers crucial for the disease’s diagnosis and treatment. Methods ITP transcriptome data and exosome-related genes (ERGs) were retrieved from public databases. Candidate genes were identified by intersecting ITP’s DEGs with exosome-related key module genes, followed by biomarker screening via machine learning and nomogram construction. Multi-dimensional analyses (enrichment, immune infiltration, drug prediction) and RT-qPCR validation were performed. Results Four biomarkers (GABARAPL1, SLC39A14, HIBADH, GSR) were confirmed, involved in spliceosome and other pathways (P < 0.05, |NES| >1). GABARAPL1, SLC39A14, HIBADH negatively correlated with activated NK cells (|cor| >0.3, P < 0.05). SLC39A14/nortriptyline and GSR/oxiglutatione showed strong binding affinity (binding free energy < -5 kcal/mol). RT-qPCR verified dysregulation of GABARAPL1, SLC39A14, GSR in ITP patients (P < 0.05). Conclusion In this study, GABARAPL1, SLC39A14, HIBADH, and GSR were successfully screened as biomarkers, and their related regulatory mechanisms were also revealed, providing innovative theoretical support for the precise diagnosis and treatment of ITP.