Serum Proteomic Profiling Uncovers LGALS3BP as a Potential Biomarker for Idiopathic Pulmonary Arterial Hypertension.

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and fatal disease characterized by pathological pulmonary vascular remodeling and right heart failure. Current biomarkers for IPAH demonstrate limited clinical utility, necessitating the discovery of noninvasive serum biomarkers to facilitate early diagnosis and prognosis. OBJECTIVE: To identify novel serum biomarkers for IPAH using tandem mass tag-based quantitative proteomics and validate their clinical relevance. METHODS: Serum samples from five IPAH patients and five age/sex-matched healthy controls (discovery cohort) were analyzed by tandem mass tag proteomics to screen differentially expressed proteins (DEPs). Functional enrichment and protein-protein interaction network analyses were performed. Serum galectin-3 binding protein (LGALS3BP) levels were validated by enzyme-linked immunosorbent assay (ELISA) in an expanded cohort (30 IPAH patients vs. 30 controls). RESULTS: Proteomic analysis identified 401 proteins and 1554 peptide fragments, with 114 DEPs between groups (47 up-regulated and 67 down-regulated). In biological processes, DEPs are primarily enriched in adaptive immune response, followed by signal transduction. Extracellular exosome and extracellular region are the most commonly enriched cell components. For molecular function, DEPs are mainly involved in antigen binding and calcium ion binding, with the top 30 Gene Ontology terms exhibiting similar distribution patterns between up- and down-regulated DEPs. Pathway analysis revealed significant enrichment in complement/coagulation cascades, immune response, and extracellular matrix remodeling. LGALS3BP was observed to be significantly up-regulated in IPAH serum compared with controls (fold change = 1.36, p < 0.001), a finding validated by independent ELISA (IPAH: 6.43 ± 1.73 μg/mL vs. controls: 2.33 ± 1.06 μg/mL; p < 0.001). CONCLUSIONS: Integrated proteomic profiling and clinical validation provide the first evidence of elevated serum LGALS3BP in IPAH, indicating its putative role in pathogenesis and translational medicine.