Abstract
BACKGROUND: Cesarean scar pregnancy (CSP) is a life-threatening condition with a rising incidence in China. The pathogenesis of CSP remains poorly understood, partly due to the limited availability of comprehensive datasets constrained by spatiotemporal factors. OBJECTIVE: This study aimed to explore key regulatory molecules and mechanisms involved in CSP through a multi-omics approach. METHODS: Proteomic analysis was performed on decidual and villous tissues from clinical patients (n = 6, including 3 CSP cases and 3 controls). Gene expression datasets (n = 9) were obtained from the GEO and SRA databases. Bioinformatics analyses were conducted using DAVID, Metascape, and STRING, with transcription factor prediction performed via the JASPAR database. Data analysis was conducted using SPSS 27, with a significance threshold set at P < 0.05. RESULTS: CSP shared differentially expressed genes (DEGs) with cesarean delivery (CD) and embryo implantation (EI). Enrichment analysis revealed that biological processes and KEGG pathways related to adhesion, with Integrin Subunit Beta 3 (ITGB3), Integrin Subunit Alpha 2b (ITGA2B), and Vitronectin (VTN) playing significant roles. ITGB3 expression was significantly downregulated following CD compared to spontaneous delivery, followed by upregulation in subsequent pregnancies. The transcription factor GATA4 was identified as a key regulator of ITGB3, potentially contributing to CSP pathogenesis. CONCLUSION: Our findings suggest that CSP development is closely associated with CD and EI, with ITGB3 and its regulatory network playing a crucial role. GATA4-mediated regulation of ITGB3 may represent an important molecular mechanism contributing to CSP formation.