Identification of key ferroptosis‑related biomarkers in Kawasaki disease by clinical and experimental validation

Kawasaki disease (KD) is an acute febrile rash that is primarily characterized by systemic vasculitis and is the leading cause of childhood-acquired heart disease. At present, a KD diagnosis is solely dependent on clinical symptoms and effective diagnostic markers are unavailable. Ferroptosis, a novel form of programmed cell death, contributes to the pathophysiology of infectious diseases. The present study aimed to identify key ferroptosis-related genes (FRGs) involved in the pathological process of KD and thus potential diagnostic biomarkers for this disease. For this purpose, differentially expressed-FRGs (DE-FRGs) between patients with KD and healthy controls were screened. The least absolute shrinkage and selection operator (LASSO) algorithm and a logistic regression model combined with receiver operating characteristic analysis were then used to identify and assess ferroptosis-related markers. Additionally, immune cell infiltration landscapes in the KD and control groups were evaluated using CIBERSORT. Moreover, the predictive value of the identified markers was validated in the clinical samples as well as vascular endothelial cells. A total of 10 DE-FRGs were screened from the KD and control samples. These 10 DE-FRGs were then applied to the LASSO model and 6 key ferroptosis-related markers were obtained. The subsequent Gene Set Variation Analysis results suggested that high expression levels of these markers were closely associated with innate immune activation and metabolism, while low expression was mainly linked to adaptive immune-related pathways. In addition to validating each gene in the training and validation sets, the diagnostic potential of these markers was assessed utilizing KD samples obtained from Shenzhen Baoan Women's and Children's Hospital. As a result, MAPK14, SLC2A3 and PGD were selected as potential diagnostic markers for KD. Additionally, changes in the expression of marker genes during inflammatory activation of vascular endothelial cells were measured by reverse transcription-quantitative PCR. The results of the present study will help to understand the role of FRGs in the pathogenesis of KD. Moreover, the identified FRGs may serve as diagnostic biomarkers, providing new strategies for KD prediction and treatment.