骨肉瘤铜死亡相关LncRNA预后模型构建与验证  

Construction and validation of prognostic model of Cuproptosis-related LncRNA in osteosarcoma

作　　者：范以东 秦刚[2] 苏国威 肖世富 刘俊良 李威材 吴广涛 FAN Yi-dong;QIN Gang;SU Guo-wei;XIAO Shi-fu;LIU Jun-liang;LI Wei-cai;WU Guang-tao(Guangxi University of Traditional Chinese Medicine,Nanning 530022,China;The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine,Nanning 530022,China)

机构地区：[1]广西中医药大学,广西南宁530022 [2]广西中医药大学第一附属医院,广西南宁530022

出　　处：《海南医学院学报》2023年第16期1233-1240,共8页Journal of Hainan Medical University

基　　金：国家自然科学基金(81860793);广西自然科学基金(2020JJA140375);广西研究生教育创新计划项目(YCSY2022027)。

摘　　要：目的:Cuproptosis是一种新发现的程序性细胞死亡形式,被认为在肿瘤治疗中起重要作用。长链非编码RNA(long non-coding RNA,lncRNA)参与调节细胞多种生理与病理活动。本研究旨在探讨铜死亡相关LncRNA在骨肉瘤中的预后意义。方法:从公共数据库UCSC Xena和GTEx数据库下载骨肉瘤样本与正常样本的基因表达谱以及相应的临床数据,从已发表的文献中获取铜死亡基因,采用共表达网络、最小绝对收缩和选择算法(LASSO)和Cox回归模型构建骨肉瘤铜死亡相关lncRNA预后模型并进行内部验证。采用受试者工作特征(ROC)曲线和列线图来评估模型的预测能力。单样本基因集富集分析(ssGSEA)探讨不同风险组与骨肉瘤免疫细胞与功能的相关性。结果:对收集到的19个铜死亡基因进行共表达分析,得到181个铜死亡相关lncRNA,差异分析及单因素Cox分析筛选出10个铜死亡预后相关的LncRNA。随后通过Lasso及多因素Cox回归筛选得到了3个铜死亡相关lncRNA(AC124798.1、AC090152.1、AC090559.1)构建预后模型。根据风险评分中位值将患者分为高、低风险组。低风险组总生存期、风险评分分布、生存状况结果优于高风险组,并在内部数据中得到了验证。单因素和多因素Cox回归分析显示,风险评分是一个独立预后因素。列线图与ROC曲线表明,该预后模型具有较好的预测能力。ssGSEA结果提示高风险组中免疫细胞及功能可能受到抑制。结论:3个铜死亡相关lncRNA可能有助于对骨肉瘤患者预后进行指导,为临床决策提供一定理论依据。Objective:To investigate the prognostic significance of Cuproptosis-associated lncRNAs in osteosarcoma.Cuproptosis is a newly discovered form of apoptotic process that is thought to play an important role in cancer therapy.Long non-coding RNA(lncRNA)is involved in regulating many physiological and pathological activities of cells.Methods:The Gene expression profiling of osteosarcoma samples versus normal samples and corresponding clinical data were downloaded from the public databases UCSC Xena and GTEx,and the Cuproptosis gene was obtained from the published literature,the prognostic model of osteosarcoma Cuproptosis-related lncRNA was constructed by using coexpression network,minimum absolute contraction and selection algorithm(LASSO)and Cox regression model.Receiver operating characteristic(ROC)curves and nomograms were used to assess the predictive power of the model.Single-sample gene set enrichment analysis(ssGSEA)was used to explore the relationship between osteosarcoma immune cells and function in different risk groups.Results:181 Cuproptosis-related lncRNAs were obtained by co-expression analysis of 19 copper death genes collected.Ten lncRNAs were screened out by differential analysis and single factor Cox analysis.Three Cuproptosis related lncRNAs(AC124798.1,AC090152.1,AC090559.1)were screened by LASSO and multivariate Cox regression to construct the prognostic model.Patients were divided into high and low risk groups based on the median risk score.The results of overall survival,risk score distribution and survival status in the low-risk group were better than those in the high-risk group,and were verified in the internal data.Univariate and multivariate Cox regression analyses showed that risk score was an independent prognostic factor.Nomograms and ROC curves showed that the prognostic model had good predictive ability.The results of ssGSEA suggest that immune cells and function may be inhibited in the high risk group.Conclusion:The 3 Cuproptosis-related lncRNAs may be helpful to guide the prognosis

关 键 词：骨肉瘤 铜死亡 lncRNA 预后模型 ssGSEA 

分 类 号：R738.1[医药卫生—肿瘤]