DNAJB11基因在尤文氏肉瘤中的表达及预后价值  

Expression and prognostic value of DNAJB11 gene in Ewing′s sarcoma

作　　者：李鑫[1] 刘震东 李昂 王红强[2] LI Xin;LIU Zhendong;LI Ang;WANG Hongqiang(Department of Surgery of Spine and Spinal Cord,Henan University People′s Hospital,Zhengzhou,Henan 450003,China;Department of Surgery of Spine and Spinal Cord,Henan Provincial People′s Hospital,Zhengzhou,Henan 450003,China)

机构地区：[1]河南大学人民医院脊柱脊髓外科,河南郑州450003 [2]河南省人民医院脊柱脊髓外科,河南郑州450003

出　　处：《国际检验医学杂志》2023年第10期1181-1187,1194,共8页International Journal of Laboratory Medicine

基　　金：河南省医学科技攻关计划省部共建项目(SB201901085)。

摘　　要：目的 探讨DnaJ热休克蛋白家族成员B11(DNAJB11)在尤文氏肉瘤(ES)中的预后、诊断价值及与免疫细胞浸润的关系,并预测具有潜在治疗价值的药物。方法 利用GEO数据库分析DNAJB11在ES样本与正常样本中的表达水平差异,并使用荧光定量PCR(RT-qPCR)进行验证。随后获取ICGC数据库中56例ES的RNA测序(RNA-seq)数据和临床相关信息进行后续分析,根据DNAJB11表达水平将患者分为高表达组、低表达组,通过“limma”包鉴定两组间的差异表达基因。采用Kaplan-Meier生存分析、单因素和多因素COX分析及受试者工作特征(ROC)曲线分析DNAJB11表达水平对ES患者预后的影响,GO和KEGG富集分析DNAJB11在ES病理进展中可能参与的生物学途径,ssGSEA算法分析DNAJB11表达水平与ES免疫细胞浸润的关系,CMap数据库筛选对ES具有治疗潜力的药物。结果 结合GEO、ICGC数据库与RT-qPCR分析结果发现,DNAJB11在ES中呈高表达(P<0.05),且DNAJB11高表达与ES发生转移有关。Kaplan-Meier生存曲线分析显示DNAJB11高表达与ES患者较差的预后相关(P=0.029)。多因素COX分析显示DNAJB11高表达是ES患者预后的独立危险因素(P=0.002,HR=1.055,95%CI:1.020~1.091)。ROC曲线分析显示,DNAJB11对ES预后有一定的预测价值。GO和KEGG富集分析显示,DNAJB11主要参与内质网应激反应、抗原加工及呈递和主要组织相容性复合体Ⅱ类蛋白复合物结合等通路。ssGSEA免疫评分结果提示DNAJB11高表达组具有较高的免疫细胞浸润丰度。CMap分析提示粗糠柴毒素、甲氟喹和依米丁可能是治疗ES的潜在治疗药物。结论 DNAJB11高表达预示患者预后较差,并对ES免疫微环境有一定的影响,DNAJB11有望成为治疗ES的新的生物靶点。Objective To investigate the prognostic and diagnostic value of DnaJ heat shock protein family member B11(DNAJB11)in Ewing′s sarcoma(ES)and its relationship with immune cell infiltration,and to predict potential therapeutic drugs.Methods Differential expression of DNAJB11 between ES and normal samples was analyzed by GEO database,and verified by fluorescence quantitative PCR(RT-qPCR).The RNA-seq data and clinical information of 56 ES cases in the ICGC database were obtained for subsequent analysis.According to the expression level of DNAJB11,the patients were divided into high and low expression groups,and the differentially expressed genes between the two groups were identified by the"limma"package.Kaplan-Meier survival analysis,univariate and multivariate COX analysis and ROC curve were used to explore the effect of DNAJB11 expression on the prognosis of ES patients.GO and KEGG enrichment analysis were used to analyze the possible biological pathways that DNAJB11 might be involved in the pathological progression of ES.The relationship between the expression of DNAJB11 and the infiltration of ES immune cells was analyzed by ssGSEA algorithm,and the drugs with therapeutic potential for ES were screened by CMap database.Results The results of GEO,ICGC database and RT-qPCR analysis showed that DNAJB11 was highly expressed in ES(P<0.05),and the high expression of DNAJB11 was associated with the metastasis of ES.Kaplan-Meier survival curve analysis showed that high expression of DNAJB11 was associated with poor prognosis in ES patients(P=0.029).Multivariate COX analysis showed that high expression of DNAJB11 was an independent risk factor for prognosis in ES patients(P=0.002,HR=1.055,95%CI:1.020-1.091).ROC curve analysis showed that DNAJB11 had certain prognostic value for ES.GO and KEGG enrichment analysis showed that DNAJB11 was mainly involved in endoplasmic reticulum stress response,antigen processing and presentation,and major histocompatibility complex ClassⅡprotein complex binding.The ssGSEA immune score r

关 键 词：尤文氏肉瘤 DnaJ热休克蛋白家族成员B11 免疫微环境 预后 

分 类 号：R738.1[医药卫生—肿瘤]