上皮间质转化（EMT）在子宫内膜癌（EC）的发展和进展中起着不可或缺的作用。然而，目前很少有证据报道EMT相关分子在EC预后中的功能和应用。本研究旨在发展EC患者预后预测的新型分子标志物。从癌症基因组图谱（TCGA）数据库中获取的EC患者的RNA测序数据用于筛选肿瘤和正常组织之间的差异表达基因（DEGs）。采用LASSO方法的Cox回归模型来识别与生存相关的DEGs，并建立了一个预测签名，该签名通过Kaplan-Meier曲线、接收者操作特征曲线（ROC）和校准曲线进行评估。最后，进行功能富集分析和细胞实验以揭示与EC进展相关的预后相关基因的作用。总共筛选出540个EC相关的EMT DEGs，并随后建立了一个由SIRT2、SIX1、CDKN2A和PGR组成的四基因风险签名来预测EC的总体生存。通过多变量Cox回归分析，该风险签名可以作为EC预后的有意义的独立指标（HR = 2.002，95%CI = 1.433-2.798；P<0.001）。将风险签名与临床特征相结合的预测图表显示出鲁棒的有效性和性能，由ROC曲线和校准曲线指示了EC总体生存。功能富集分析显示，EMT相关基因风险签名与细胞外基质组织、间充质发育和细胞组分形态发育有关，表明其可能与上皮间质转化和癌症进展相关。在功能方面，我们证明了SIX1、SIRT2和CDKN2A表达的沉默可以加速肿瘤细胞的迁移和入侵能力，而PGR的下调则显著抑制了癌细胞的迁移和入侵。总的来说，一种新的四个EMT相关基因的签名是EC预后的潜在生物标志物。这些发现可能有助于改善EC患者的个体化预后预测和治疗。© 2023. BioMed Central Ltd.，Springer Nature的一部分。

The epithelial-mesenchymal transition (EMT) plays an indispensable role in the development and progression of Endometrial cancer (EC). Nevertheless, little evidence is reported to uncover the functionality and application of EMT-related molecules in the prognosis of EC. This study aims to develop novel molecular markers for prognosis prediction in patients with EC.RNA sequencing profiles of EC patients obtained from The Cancer Genome Atlas (TCGA) database were used to screen differential expression genes (DEGs) between tumors and normal tissues. The Cox regression model with the LASSO method was utilized to identify survival-related DEGs and to establish a prognostic signature whose performance was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC) and calibration curve. Eventually, functional enrichment analysis and cellular experiments were performed to reveal the roles of prognosis-related genes in EC progression.A total of 540 EMT-related DEGs in EC were screened, and subsequently a four-gene risk signature comprising SIRT2, SIX1, CDKN2A and PGR was established to predict overall survival of EC. This risk signature could serve as a meaningfully independent indicator for EC prognosis via multivariate Cox regression (HR = 2.002, 95%CI = 1.433-2.798; P < 0.001). The nomogram integrating the risk signature and clinical characteristics exhibited robust validity and performance at predicting EC overall survival indicated by ROC and calibration curve. Functional enrichment analysis revealed that the EMT-related genes risk signature was associated with extracellular matrix organization, mesenchymal development and cellular component morphogenesis, suggesting its possible relevance to epithelial-mesenchymal transition and cancer progression. Functionally, we demonstrated that the silencing of SIX1, SIRT2 and CDKN2A expression could accelerate the migratory and invasive capacities of tumor cells, whereas the downregulation of PGR dramatically inhibited cancer cells migration and invasion.Altogether, a novel four-EMT-related genes signature was a potential biomarker for EC prognosis. These findings might help to ameliorate the individualized prognostication and therapeutic treatment of EC patients.© 2023. BioMed Central Ltd., part of Springer Nature.