Zhao Peng, Chang Junli, Chen YeKai, Sun Xingyuan, Ma Xiaoping, Zhou Chujie, Zhou Lei, Wang Yongjun, Yang Yanping
Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032 China.
Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, 200032 China.
Phenomics. 2024 Jul 8;4(5):430-452. doi: 10.1007/s43657-023-00132-y. eCollection 2024 Oct.
Osteosarcoma is the most common malignant bone tumor and is frequently diagnosed in juvenile. Cellular senescence is a fundamental hallmark of osteosarcoma and plays a vital role in the initiation and progression of aging and tumorigenesis. Long non-coding RNAs (lncRNAs) are implicated in tumorigenesis. In this study, six cellular senescence-related lncRNAs with independent prognostic significance in juvenile osteosarcoma patients were identified through univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression analysis, and multivariate Cox regression analysis. Prognostic significance was further confirmed by Kaplan-Meier (KM) survival curves, co-expression interaction networks, and sankey diagrams. A prognostic model of cellular senescence-related genes in juvenile osteosarcoma patients was then constructed using multivariate Cox regression analysis based on these six genes. High- and low-risk groups were identified according to the median risk score calculated by the prognostic model. The favorable prognostic significance of this model was demonstrated through survival curves, receiver operating characteristic (ROC) curves, distribution scatter plots and lncRNA expression heatmaps. Furthermore, cellular senescence-related lncRNAs were validated by enrichment analysis, immunological correlation analysis, mA correlation analysis, and drug sensitivity correlation analysis. These findings are important for improving the prognosis of juvenile osteosarcoma patients and understanding the mechanisms underlying cellular senescence in juvenile osteosarcoma development.
骨肉瘤是最常见的恶性骨肿瘤，常于青少年期被诊断出来。细胞衰老乃是骨肉瘤的一个基本特征，在衰老及肿瘤发生的起始与进展过程中发挥着至关重要的作用。长链非编码RNA（lncRNAs）与肿瘤发生有关。在本研究中，通过单因素Cox回归分析、最小绝对收缩和选择算子（LASSO）回归分析以及多因素Cox回归分析，在青少年骨肉瘤患者中鉴定出六个具有独立预后意义的细胞衰老相关lncRNAs。通过Kaplan-Meier（KM）生存曲线、共表达相互作用网络和桑基图进一步证实了预后意义。然后基于这六个基因，使用多因素Cox回归分析构建了青少年骨肉瘤患者细胞衰老相关基因的预后模型。根据预后模型计算出的中位风险评分确定高风险组和低风险组。通过生存曲线、受试者工作特征（ROC）曲线、分布散点图和lncRNA表达热图证明了该模型具有良好的预后意义。此外，通过富集分析、免疫相关性分析、mA相关性分析和药物敏感性相关性分析对细胞衰老相关lncRNAs进行了验证。这些发现对于改善青少年骨肉瘤患者的预后以及理解青少年骨肉瘤发生发展过程中细胞衰老的潜在机制具有重要意义。
