Cell-type-specific regulators landscape and regulatory mechanisms underlying pyroptosis in uterine corpus endometrial...

Background: Endometrial cancer (UCEC) has a significant detrimental effect on patient quality of life. Although pyroptosis-related genes have been reported to contribute to tumor pathogenesis, the specific mechanism of pyroptosis in patients with UCEC remains elusive. Methods: We provide an overview of the landscape of pyroptosis-related genes in UCEC tissues through single-cell RNA sequencing (scRNA-Seq) datasets from the tissues of UCEC of 6089 cells. In addition, pyroptosis-related gene expression pattern was verified based on the RNA-Seq datasets, and observation of abnormal pathological characteristics of UCEC tissue. Results: The pyroptosis-related gene IL-6 is specifically upregulated in epithelial cells and dysregulates cell population proliferation and enhances apoptosis. The upregulation of BAX and TNF expression in macrophages induces infiltration of aberrantly activated macrophages, which display dysfunctional differentiation in tumor tissues, altered immune responses, and activation of the tumor necrosis factor (TNF) pathway in UCEC macrophages. In addition, dysregulation of pyroptosis-related genes induces aberrant cell-cell communication in tumor tissues and mediates ligand-receptor interactions between various cell types in UCEC via the TNF signaling pathway to promote cancer progression. Quantitative real-time (PCR) and immunohistochemistry were used for the in vitro experimental validation. Conclusion: Pyroptosis-related genes can serve as biomarkers for UCEC, playing a role in early disease diagnosis, helping to predict patient prognosis, and guiding the selection of personalized treatment options.