ArticleClinical proteomics2025
Identification of adrenocorticotropic hormone-specific therapeutic biomarkers in infantile epileptic spasm syndrome using data-independent acquisition mass spectrometry.
Article in Clinical proteomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundInfantile epileptic spasm syndrome (IESS) presents significant therapeutic challenges, with the molecular mechanisms underlying variable responses to adrenocorticotropic hormone (ACTH) remaining poorly understood. This study aimed to identify ACTH-specific therapeutic biomarkers in IESS patients with effective (EF) and ineffective (IEF) responses to ACTH, providing potential clues for therapeutic interventions and insights into IESS pathogenesis.
methodsSixty IESS patients were recruited and allocated into the EF group (n = 30) and IEF group (n = 30), alongside 40 age- and gender-matched healthy controls. Plasma samples were analyzed using data-independent acquisition (DIA) proteomics to identify differentially expressed proteins (DEPs). Functional annotation of DEPs was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Receiver operating characteristic (ROC) curve analysis was employed to construct a diagnostic biomarker model. Enzyme-linked immunosorbent assay (ELISA) validation ensured the robustness of our findings.
resultsA total of 114 proteins were identified as uniquely associated with the EF group. GO and KEGG analyses revealed DEPs in pathways related to humoral immune response regulation, phagocytosis, complement and coagulation cascades, and metabolic processes. ROC curve analysis highlighted complement component 8 beta (C8β), Plasminogen (PLG), Haptoglobin (HP), Aldolase A (ALDOA), and Collagen Type XVIII Alpha 1 (COL18A1) as potential predictive biomarkers for ACTH efficacy, each achieving an area under the curve value above 0.8. Quantitative ELISA validation confirmed higher levels of C8β and PLG, and lower levels of HP, ALDOA, and COL18A1, in the EF group compared to the IEF group, consistent with the DIA results.
conclusionsThese findings offer novel insights into the molecular mechanisms underlying ACTH response variability in IESS and propose candidate plasma protein biomarkers for predicting ACTH treatment efficacy. This study, combining DIA-MS proteomics with targeted ELISA validation in plasma from individuals with IESS, provides evidence that the identified proteins warrant further investigation as candidate biomarkers to refine therapeutic strategies and monitor patient responses.
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