Li Meng-Pan, Long Si-Ping, Liu Wen-Cai, Long Kun, Gao Xing-Hua
Department of Orthopedics, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China.
Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Pharmacol. 2024 Aug 7;15:1419040. doi: 10.3389/fphar.2024.1419040. eCollection 2024.
Osteosarcoma (OS), a bone tumor with high ability of invasion and metastasis, has seriously affected the health of children and adolescents. Many studies have suggested a connection between OS and the epithelial-mesenchymal transition (EMT). We aimed to integrate EMT-Related genes (EMT-RGs) to predict the prognosis, immune infiltration, and therapeutic response of patients with OS.
We used consensus clustering to identify potential EMT-Related OS molecular subtypes. Somatic mutation, tumor immune microenvironment, and functional enrichment analyses were performed for each subtype. We next constructed an EMT-Related risk signature and evaluated it by Kaplan-Meier (K-M) analysis survival and receiver operating characteristic (ROC) curves. Moreover, we constructed a nomogram to more accurately predict OS patients' clinical outcomes. Response effects of immunotherapy in OS patients was analyzed by Tumor Immune Dysfunction and Exclusion (TIDE) analysis, while sensitivity for chemotherapeutic agents was analyzed using oncoPredict. Finally, the expression patterns of hub genes were investigated by single-cell RNA sequencing (scRNA-seq) data analysis.
A total of 53 EMT-RDGs related to prognosis were identified, separating OS samples into two separate subgroups. The EMT-high subgroup showed favourable overall survival and more active immune response. Significant correlations were found between EMT-Related DEGs and functions as well as pathways linked to the development of OS. Additionally, a risk signature was established and OS patients were divided into two categories based on the risk scores. The signature presented a good predictive performance and could be recognized as an independent predictive factor for OS. Furthermore, patients with higher risk scores exhibited better sensitivity for five drugs, while no significant difference existed in immunotherapy response between the two risk subgroups. scRNA-seq data analysis displayed different expression patterns of the hub genes.
We developed a novel EMT-Related risk signature that can be considered as an independent predictor for OS, which may help improve clinical outcome prediction and guide personalized treatments for patients with OS.
骨肉瘤（OS）是一种具有高侵袭和转移能力的骨肿瘤，严重影响儿童和青少年的健康。许多研究表明骨肉瘤与上皮-间质转化（EMT）之间存在联系。我们旨在整合与EMT相关的基因（EMT-RGs）来预测骨肉瘤患者的预后、免疫浸润和治疗反应。
我们使用一致性聚类来识别潜在的与EMT相关的骨肉瘤分子亚型。对每个亚型进行体细胞突变、肿瘤免疫微环境和功能富集分析。接下来，我们构建了一个与EMT相关的风险特征，并通过Kaplan-Meier（K-M）生存分析和受试者工作特征（ROC）曲线对其进行评估。此外，我们构建了一个列线图以更准确地预测骨肉瘤患者的临床结局。通过肿瘤免疫功能障碍和排除（TIDE）分析来分析免疫疗法在骨肉瘤患者中的反应效果，而使用oncoPredict分析对化疗药物的敏感性。最后，通过单细胞RNA测序（scRNA-seq）数据分析来研究枢纽基因的表达模式。
共鉴定出53个与预后相关的EMT-RDGs，将骨肉瘤样本分为两个独立的亚组。EMT高亚组显示出良好的总生存期和更活跃的免疫反应。发现与EMT相关的差异表达基因（DEGs）与骨肉瘤发生发展相关的功能和通路之间存在显著相关性。此外，建立了一个风险特征，并根据风险评分将骨肉瘤患者分为两类。该特征表现出良好的预测性能，可被视为骨肉瘤的独立预测因素。此外，风险评分较高的患者对五种药物表现出更好的敏感性，而两个风险亚组之间在免疫治疗反应方面没有显著差异。scRNA-seq数据分析显示了枢纽基因的不同表达模式。
我们开发了一种新的与EMT相关的风险特征，可被视为骨肉瘤的独立预测指标，这可能有助于改善临床结局预测并指导骨肉瘤患者的个性化治疗。
