Identification of Serum BST1 as a Biomarker to Predict Coronary Artery Lesions in Children with Kawasaki Disease Based on 4D-DIA Quantitative Proteomics

Shuwan Zhang,1,2 Junhua Huang,3 Mengfei Zhang,2 Chuanmei Zhao,2 Wenjing Wu,1 Wei Chen1 1Department of Laboratory Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Clinical Laboratory, Xi’an Children’s Hospital, Xi’an, Shaanxi, People’s Republic of China; 3School of Medical Technology, Xi’an Medical University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Wei Chen, Department of Laboratory Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China, Email chenweixjtu2014@126.comBackground: Kawasaki disease (KD) is a leading cause of acquired heart disease in children, with coronary artery lesions (CAL) as its most severe complication. This observational study aimed to investigate the expression of bone marrow stromal cell antigen-1 (BST1) in KD patients and its value for predicting CAL.Methods: Serum samples were collected from KD patients before intravenous immunoglobulin (IVIG) treatment and healthy controls (HC) in Xi’an Children’s Hospital from July 2023 to August 2024. KD Patients were stratified into CAL and non-CAL (nCAL) groups based on echocardiography. In the discovery cohort (8 KD-CAL patients, 7 KD-nCAL patients, and 4 HC), Sera were analyzed via four-dimensional data-independent acquisition (4D-DIA) quantitative proteomics. Differentially expressed proteins (DEPs) were identified and analyzed for bioinformatics. In the validation cohort (35 KD-CAL patients, 61 KD-nCAL patients, and 30 HC), serum BST1 was validated by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve was constructed to assess the performance of BST1 in predicting CAL.Results: A total of 2575 proteins were identified by 4D-DIA proteomics, with 807 DEPs in nCAL vs HC and 883 DEPs in CAL vs HC. Compared to nCAL, 213 DEPs were identified in CAL patients, among which BST1 was significantly upregulated only in the CAL group. Functional analyses revealed enrichment in innate immune response, cell adhesion, RNA processing pathways, complement and coagulation cascades, extracellular exosomes, and cellular metabolism. ELISA confirmation showed elevated BST1 levels in CAL patients, which positively correlated with Z-scores. ROC analysis demonstrated high prognostic accuracy for CAL (AUC=0.9052).Conclusion: Serum BST1 has the potential to be a predictive biomarker for CAL in KD patients.Keywords: Kawasaki disease, CAL, KD-CAL, BST1, proteomics, 4D-DIA, ROC curve