PDF(Pubmed)
Abstract：
Osteosarcoma (OS) is a heterogeneous malignant spindle cell tumor that is aggressive and has a poor prognosis. Although combining surgery and chemotherapy has significantly improved patient outcomes, the prognosis for OS patients with metastatic or recurrent OS has remained unsatisfactory. Therefore, it is imperative to gain a fresh perspective on OS development mechanisms and treatment strategies. After studying single-cell RNA sequencing (scRNA-seq) data in public databases, we identified seven OS subclonal types based on intra-tumor heterogeneity. Subsequently, we constructed a prognostic model based on pro-protein synthesis osteosarcoma (PPS-OS)-associated genes. Correlation analysis showed that the prognostic model performs extremely well in predicting OS patient prognosis. We also demonstrated that the independent risk factors for the prognosis of OS patients were tumor primary site, metastatic status, and risk score. Based on these factors, nomograms were constructed for predicting the 3- and 5-year survival rates. Afterward, the investigation of the tumor immune microenvironment (TIME) revealed the vital roles of γδ T-cell and B-cell activation. Drug sensitivity analysis and immune checkpoint analysis identified drugs that have potential application value in OS. Finally, the jumping translocation breakpoint (JTB) gene was selected for experimental validation. JTB silencing suppressed the proliferation, migration, and invasion of OS cells. Therefore, our research suggests that PPS-OS-related genes facilitate the malignant progression of OS and may be employed as prognostic indicators and therapeutic targets in OS.
摘要：
骨肉瘤（OS）是一种异质性的恶性梭形细胞肿瘤，具有侵袭性，预后不良。尽管手术和化疗相结合显著改善了患者的预后，有转移性或复发性OS的OS患者的预后仍不令人满意.因此,必须对OS开发机制和处理策略有一个全新的视角。在研究了公共数据库中的单细胞RNA测序（scRNA-seq）数据之后，我们根据肿瘤内异质性确定了7种OS亚克隆类型.随后，我们构建了基于前蛋白合成骨肉瘤(PPS-OS)相关基因的预后模型.相关分析表明，该预后模型在预测OS患者预后方面表现得非常好。我们还证明了OS患者预后的独立危险因素是肿瘤原发部位,转移状态，和风险评分。基于这些因素,列线图用于预测3年和5年生存率。之后,对肿瘤免疫微环境（TIME）的研究揭示了γδT细胞和B细胞活化的重要作用。药物敏感性分析和免疫检查点分析确定了在OS中具有潜在应用价值的药物。最后,选择跳跃易位断点(JTB)基因进行实验验证.JTB沉默抑制了增殖，迁移,和OS细胞的入侵。因此,我们的研究提示,PPS-OS相关基因促进OS的恶性进展,可作为OS的预后指标和治疗靶点.
