D106-10 Integrated Plasma Proteomics and Metabolomics Indentified Energy and Lipid Metabolic Alterations in Pulmonary Arterial Hypertension

Background Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular remodeling and right heart failure, and accumulating evidence suggests that metabolic reprogramming is an important driver of disease progression. However, intergrative multi-omics data at the plasma level remain limited. We sought to characterize systemic metabolic and protein alterations in PAH compared with healthy controls to identify disease-related pathways and candidate biomarkers. Methods In this study, 100 individuals were enrolled, including 70 patients with PAH (mean age 34.5 years, 80% female) and 30 age- and sex-matched healthy controls (mean age 34.5 years, 82.86% female). Plasma samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for untargeted proteomics. Differentially expressed proteins (DEPs) and differentially abundant metabolites (DAMs) between PAH and controls were indentified, followed by KEGG pathway enrichment to delineate dysregulated metabolic networks. To prioritize markers with diagnostic potential, a Boruta machine-learning algorithm was applied to the integrated dataset. Results Integrated analysis identified 86 DEPs and 28 DAMs that significantly distinguished PAH from controls. KEGG enrichment of DEPs revealed perturbations in energy metabolism pathways, including glycolysis / gluconeogenesis and carbon metabolism, indicating a shift toward metabolic reprogramming. Meanwhile, DAMs were prominently enriched in amino acid, lipid metabolism, and tricarboxylic acid cycle, further supporting a critical role of altered energy utilization in PAH. Feature selection using machine learning-based BORUTA algorithm yielded a 10-analyte panel with high importance for group separation—including (9Z,12Z,15Z)-Octadecatrienoic acid, Inosine, LDHA, Hexadecanoic acid, Linoleate, HP, 9(10)-EpOME, (9Z)-Octadecenoic acid, UBTF and sn-Glycero-3-phosphocholine, that present a excellent plasma-based discrimination of PAH (AUC=0.9). Conclusion Plasma-based integrated proteomics and metabolomics demostrated that PAH is associated with coordinated alterations in energy, amino acid, and lipid metabolism in the circulation. These indentified 10-analyte panel prioritized a set of candicdate circulating markers that may provide valuable insights into the mechanisms underlying PAH and further development of minimally invasive biomarkers in PAH. This abstract is funded by: This work was supported by the Program of National Key Research and Development projects of China (2023YFC2509500) and the Program of National Natural Science Foundation of China (82570413), the Noncommunicable Chronic Diseases-National Science and Technology Major Project (2024ZD0526700, 2024ZD0528600), the the Pujiang Talent Program (22OHD064), and the Program of Shanghai Pulmonary Hospital (2025-0554-YB-15, LYRC202415).