上皮间充质转化（EMT）与骨肉瘤（OS）之间的相关性已被广泛报道。整合与EMT有关的基因以预测预后对于研究OS中EMT机制具有重要意义。本研究旨在构建适用于OS的预后EMT相关基因特征。从治疗适用性研究以产生有效治疗（TARGET）和基因表达测序芯片数据库（GEO）下载了OS患者的转录组和生存数据。我们进行了单变量Cox回归、最小绝对收缩和选择算子（LASSO）回归和阶梯多元Cox回归分析，以构建EMT相关基因特征。应用Kaplan-Meier分析和时间相关ROC评估其预测性能。 GSVA, ssGSEA, ESTIMATE, 和scRNA-seq, 进一步研究肿瘤微环境，还研究了药物IC50和ERG分数之间的相关性。此外，还进行了Edu和Transwell实验以评估OS细胞的恶性程度。我们构建了一个新颖的EMT相关基因特征（包括CDK3、MYC、UHRF2、STC2、COL5A2、MMD和EHMT2）以预测OS的预后。根据特征，分层为高ERG和低ERG评分组的患者表现出明显不同的预后。ROC曲线和Kaplan-Meier分析显示了该特征具有良好的预测性能并进行了外部验证。GSVA, ssGSEA, ESTIMATE算法和scRNA-seq挖掘了EMT相关途径，并表明ERG评分与免疫激活之间的相关性。值得注意的是，关键基因CDK3在OS组织中上调，并与OS细胞的增殖和迁移呈正相关。我们的EMT相关基因特征可能作为独立的预后因子，参考OS风险分层并指导临床策略。© 2023 John Wiley＆Sons Ltd发表的《癌症医学》。

The correlation between epithelial-mesenchymal transition (EMT) and osteosarcoma (OS) has been widely reported. Integration of the EMT-related genes to predict the prognosis is significant for investigating the mechanism of EMT in OS. Here, we aimed to construct a prognostic EMT-related gene signature for OS.Transcriptomic and survival data of OS patients were downloaded from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO). We performed univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and stepwise multivariate Cox regression analysis to construct EMT-related gene signatures. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) were applied to evaluate its predictive performance. GSVA, ssGSEA, ESTIMATE, and scRNA-seq were performed to investigate the tumor microenvironment, and the correlation between IC50 of drugs and ERG score was investigated. Furthermore, Edu and transwell experiments were conducted to assess the malignancy of OS cells.We constructed a novel EMT-related gene signature (including CDK3, MYC, UHRF2, STC2, COL5A2, MMD, and EHMT2) for outcome prediction of OS. According to the signature, patients stratified into high- and low-ERG-score groups exhibited significantly different prognoses. ROC curves and Kaplan-Meier analysis revealed a promising performance of the signature with external validation. GSVA, ssGSEA, ESTIMATE algorithm, and scRNA-seq excavated EMT-related pathways and suggested the correlation between ERG score and immune activation. Notably, the pivotal gene CDK3 was upregulated in OS tissue and positively related to OS cell proliferation and migration.Our EMT-related gene signature might reference OS risk stratification and guide clinical strategies as an independent prognostic factor in OS.© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.