Guo Hongrui, Qin Wufeng, Li Jinpeng, Wang Fucheng, Yang Jiaolin, Wang Yaling, Zhang Xinglin, Ding Yuanyuan, Ting Kaiwen, Li Xia, Ji Jingru, Han Yanyan, Hui Ailing, Su Huancheng, Zhang Sanyuan, Wang Zhe
Shanxi Medical University, Taiyuan 030001, China.
Department of Gynecology, First Hospital of Shanxi Medical University, Taiyuan 030001, China.
J Cancer. 2025 Jan 1;16(2):660-679. doi: 10.7150/jca.100547. eCollection 2025.
: 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. 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. The pyroptosis-related gene is specifically upregulated in epithelial cells and dysregulates cell population proliferation and enhances apoptosis. The upregulation of and 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 signaling pathway to promote cancer progression. Quantitative real-time (PCR) and immunohistochemistry were used for the experimental validation. 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.
子宫内膜癌（UCEC）对患者生活质量有显著不利影响。尽管据报道焦亡相关基因有助于肿瘤发病机制，但UCEC患者中焦亡的具体机制仍不清楚。我们通过对来自6089个UCEC组织细胞的单细胞RNA测序（scRNA-Seq）数据集，概述了UCEC组织中焦亡相关基因的情况。此外，基于RNA-Seq数据集以及对UCEC组织异常病理特征的观察，验证了焦亡相关基因的表达模式。焦亡相关基因在上皮细胞中特异性上调，失调细胞群体增殖并增强凋亡。巨噬细胞中该基因和另一基因表达的上调诱导异常激活巨噬细胞的浸润，这些巨噬细胞在肿瘤组织中表现出功能失调的分化、改变的免疫反应以及UCEC巨噬细胞中肿瘤坏死因子（TNF）途径的激活。此外，焦亡相关基因的失调诱导肿瘤组织中异常的细胞间通讯，并通过该信号通路介导UCEC中各种细胞类型之间的配体-受体相互作用以促进癌症进展。采用定量实时（PCR）和免疫组织化学进行实验验证。焦亡相关基因可作为UCEC的生物标志物，在疾病早期诊断中发挥作用，有助于预测患者预后，并指导个性化治疗方案的选择。
