首页|骨肉瘤中铜死亡相关亚型鉴定、预后模型构建以及免疫细胞浸润分析

骨肉瘤中铜死亡相关亚型鉴定、预后模型构建以及免疫细胞浸润分析

扫码查看
目的:在铜死亡基因基础上分析骨肉瘤(OS)中铜死亡基因相关亚型鉴定、预后模型构建和免疫浸润的影响.方法:联合TARGET与GEO数据库对OS相关铜死亡基因进行生存分析及预后相关性分析.采用一致性聚类方法将OS分为铜死亡不同亚型.运用SSGSEA对铜死亡分型进行免疫细胞差异分析.设置P value=0.05和q value=0.05,对铜死亡分型的差异基因进行GO及KEGG富集分析.依据Lasso回归分析及交叉验证结果构建预后模型,并进行风险评估分析和运用ROC曲线评估模型预测准确性.结合临床性状构建列线图预测患者生存期,同时进行风险差异分析.对OS样本进行免疫细胞浸润和肿瘤微环境分析.运用R软件"pRRophetic"包对OS样本进行药物敏感性分析.结果:确定FDX1、GLS、DLAT和PDHB为OS预后的高风险基因.对OS样本进行铜死亡分型,可将OS分为两型:CRGclusterA与CRGclusterB,其中CRGclusterA与Th2细胞相关,CRGclusterB与Th1细胞相关.大部分OS铜死亡基因在CRGclusterA中呈高表达.免疫细胞浸润分析结果表明γδ T细胞、静息肥大细胞和静息树突状细胞与风险评分呈正相关,而CD8 T细胞与风险评分呈负相关.药物敏感性分析显示OS对Elesclomol与GW.441756更敏感.结论:本研究识别出CRGclusterA与CRGclusterB两种亚型.鉴定出4个预后高风险基因:FDX1、GLS、DLAT和PDHB,为OS预后评估和免疫治疗候选靶点提供了新见解.
Identification of copper death related subtypes,construction of prognosis model and analysis of immune cell infiltration in osteosarcoma
Objective:To analyze identification of copper death gene related subtypes,construction of prognosis model and influence of immune infiltration in osteosarcoma(OS)on basis of copper death gene.Methods:Survival and prognosis of OS associated copper death gene were analyzed combining by TARGET and GEO database.OS was divided into different subtypes of copper death by consistent clustering method.SSGSEA was used to analyze difference of immune cells in classification of copper death.Setting P value= 0.05 and q value=0.05,GO and KEGG enrichment analysis were performed on differential genes of copper death typing.Prognosis model was constructed according to results of Lasso regression analysis and cross validation,risk assessment analysis and ROC curve were used to evaluate accuracy of model prediction.Combined with clinical characteristics,nomograms were constructed to predict survival time of patients,and risk differences were analyzed.Immune cell infiltration and tumor microenvironment analysis were performed on OS samples."pRRophetic"package in R software was used to analyze drug sensitivity of OS samples.Results:FDX1,GLS,DLAT and PDHB as high-risk genes for OS prognosis were identified.According to copper death classification of OS samples,OS could be divided into two types:CRGclusterA and CRGclusterB.CRGclusterA was associated with Th2 cells,and CRGclusterB was associated with Th1 cells.Most OS copper death genes were highly expressed in CRGclusterA.Immune cell infiltration analysis results showed that γδ T cells,resting mast cells and resting dendritic cells were positively correlated with risk score,while CD8 T cells were negatively correlated with risk score.Drug sensitivity analysis showed that OS showed higher sensitivity to Elesclomol and GW.441756.Conclusion:Two subtypes of CRGclusterA and CRGclusterB are identified in this study.Four high-risk prognostic genes FDX1,GLS,DLAT and PDHB are identified,providing new insights into prognostic evaluation and immunotherapy target candidates for OS.

Copper-induced cell deathOsteosarcomaConsistent clustersImmune infiltrationPrognostic model

邵子晨、李华南、章晓云、孙伟康、袁启鹏

展开 >

江西中医药大学临床医学院,南昌 330004

江西中医药大学附属医院,南昌 330004

广西中医药大学附属瑞康医院骨科,南宁 530011

铜诱导细胞死亡 骨肉瘤 一致性聚类 免疫浸润 预后模型

国家自然科学基金国家自然科学基金江西省自然科学基金

820608718186085720202BAB206071

2024

中国免疫学杂志
中国免疫学会,吉林省医学期刊社

中国免疫学杂志

CSTPCD北大核心
影响因子:0.926
ISSN:1000-484X
年,卷(期):2024.40(1)
  • 2