Xiao Bo, Liu Liyan, Chen Zhuoyuan, Li Aoyu, Xia Yu, Wang Pingxiao, Xiang Cheng, Zeng Yi, Li Hui
Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, China.
Orthopedic Biomedical Materials Engineering Laboratory of Hunan Province, Changsha, China.
Front Cell Dev Biol. 2021 Oct 18;9:753414. doi: 10.3389/fcell.2021.753414. eCollection 2021.
Osteosarcoma is the most general bone malignancy that mostly affects children and adolescents. Numerous stem cell-related genes have been founded in distinct forms of cancer. This study aimed at identifying a stem cell-related gene model for the expected assessment of the prognosis of osteosarcoma patients. We obtained the genes expression data and relevant clinical materials from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. We identified differentially expressed genes (DEGs) from the GEO dataset, whereas prognostic stem cell-related genes were obtained from the TARGET database. Subsequently, univariate, LASSO and multivariate Cox regression analyses were applied to establish the stem cell-related signature. Finally, the prognostic value of the signature was validated in the GEO dataset. Twenty-five genes were prognostic ferroptosis-related DEGs. Consequently, we identified eight stem cell-related genes as a signature of prognosis of osteosarcoma patients. Then, the Kaplan-Meier (K-M) curve, the AUC value of ROC, and Cox regression analysis verified that the eight stem cell-related gene model were a new and substantial prognostic marker independent of other clinical traits. Moreover, the nomogram on the foundation of risk score and other clinical traits was established for predicting the survival rate of osteosarcoma patients. Biological function analyses displayed that tumor related pathways were affluent. The expression level of stem cell-related genes offers novel prognostic markers as well as underlying therapeutic targets for the therapy and prevention of osteosarcoma.
骨肉瘤是最常见的骨恶性肿瘤，主要影响儿童和青少年。许多与干细胞相关的基因已在不同类型的癌症中被发现。本研究旨在确定一个与干细胞相关的基因模型，用于骨肉瘤患者预后的预期评估。我们从“生成有效治疗的治疗性应用研究”（TARGET）和基因表达综合数据库（GEO）中获取了基因表达数据和相关临床资料。我们从GEO数据集中鉴定出差异表达基因（DEG），而从TARGET数据库中获得与预后相关的干细胞基因。随后，应用单变量、LASSO和多变量Cox回归分析来建立与干细胞相关的特征。最后，在GEO数据集中验证了该特征的预后价值。25个基因是与铁死亡相关的预后DEG。因此，我们鉴定出8个与干细胞相关的基因作为骨肉瘤患者预后的特征。然后，Kaplan-Meier（K-M）曲线、ROC的AUC值和Cox回归分析证实，这8个与干细胞相关的基因模型是一个新的、独立于其他临床特征的重要预后标志物。此外，基于风险评分和其他临床特征建立了列线图，用于预测骨肉瘤患者的生存率。生物学功能分析显示，肿瘤相关通路丰富。与干细胞相关的基因表达水平为骨肉瘤的治疗和预防提供了新的预后标志物以及潜在的治疗靶点。
