Identification of diagnostic biomarkers and therapeutic targets for abdominal aortic aneurysms based on disulfidptosis mechanism

Currently, there is a lack of hallmark diagnostic markers for abdominal aortic aneurysms (AAA). Recent evidence has suggested the efficacy of gene signature related to Disulfidptosis (a novel form of regulated cell death triggered by disulfide stress) for prognostic implication. Accordingly, our current study aims to identify some relevant markers for AAA not only for understanding its pathogenesis but also for improving treatment. Abnormal cell types in AAA were initially analyzed using single-cell RNA sequencing (scRNA-seq) to select differentially expressed genes (DEGs). Then, SLC7A11 -related genes were identified using RNA sequencing (RNA-seq) data and disulfidptosis genes. AAA-related key genes were screened based on their expression patterns. Protein-Protein Interaction Networks (PPI) were then employed to identify interacting genes and predict potential therapeutic agents for AAA. Finally, the role of LCP1 in AAA progression was validated through in vitro cellular assays. Compared to control samples, the number of macrophages/monocytes was the highest in AAA, suggesting that these cells were the key immune cells during AAA progression. Three overlapping genes ( LCP1 , MARCKS , and PTPRC ) were screened, and the expression patterns of LCP1 and PTPRC were consistent in multiple datasets. LCP1 and PTPRC showed an accurate diagnostic ability (AUC > 0.76) and were therefore considered as key genes in the disulfidptosis signature. Additionally, we observed strong and robust binding interactions between 1-METHYL-5-(2-PHENOXYMETHYL-PYRROLIDINE-1-SULFONYL)-1H-INDOLE-2,3-DIONE-PTPRC, as well as between Nandrolone- phenpropionate-LCP1 and PTPRC, indicating their potential as therapeutic targets for AAA. Cellular assays confirmed that inhibition of LCP1 suppressed the expressions of inflammatory factors in AAA. This research offered novel insights into the mechanisms of AAA progression based on disulfidptosis and discovered effective biomarkers for predicting the prognosis of AAA.