Sepsis-related immune signature C3 in endometrial carcinoma: implications for prognosis, tumor progression through bioinformatics and experimental validation

Background: Sepsis and uterine corpus endometrial carcinoma (UCEC) share significant immunological and molecular pathways, particularly involving dysregulated inflammatory responses and immune modulation. Although sepsis-induced organ dysfunction is well studied, its role in cancer progression, particularly in UCEC, remains poorly understood. Purpose: This study investigated the sepsis-related immune signature (SRIS) C3 in UCEC to uncover its role in tumor progression and metastasis. Methods: RNA sequencing and clinical data from TCGA and GEO databases were analyzed using R software to identify DESRGs. Survival analysis, GO, KEGG pathway, and GSEA were performed to elucidate C3’s biological functions. PPI networks, mutational analysis, methylation profiling, and immune infiltration analysis were conducted using various bioinformatics tools. MTT assays, RT-PCR, qPCR, and wound healing assays were performed to validate C3’s function in HEC-1-B. Results: Downregulation of C3 expression in UCEC was associated with enhanced inflammation, immune evasion, and metastatic potential, showing mechanisms observed in sepsis-induced organ dysfunction. Pathway enrichment analysis revealed significant activation of the NF-κB, JAK-STAT, and complement cascades, contributing to a pro-tumorigenic microenvironment. Mutational analysis showed a significant contribution to UCEC development. Protein-protein interaction analysis demonstrated a positive correlation with SRISs. These findings highlight the pivotal role of sepsis-related immune pathways, mainly C3, in driving UCEC progression. Conclusion: Understanding the molecular interplay between sepsis-related immune responses and tumor progression may offer novel therapeutic opportunities. Specifically, targeting C3 may provide a new treatment strategy for UCEC patients with a history of sepsis, thereby improving clinical outcomes and guiding personalized therapeutic interventions.