目的探索间变性胶质细胞瘤中有预后价值的免疫浸润相关基因。方法下载TCGA(The Cancer Genome Atlas)数据库中转录组数据,量化间变性胶质细胞瘤样本的免疫浸润情况,并分为低、中、高免疫浸润组,进而对组间的差异基因进行分析,筛选出预...目的探索间变性胶质细胞瘤中有预后价值的免疫浸润相关基因。方法下载TCGA(The Cancer Genome Atlas)数据库中转录组数据,量化间变性胶质细胞瘤样本的免疫浸润情况,并分为低、中、高免疫浸润组,进而对组间的差异基因进行分析,筛选出预后相关的核心基因ZAP70。研究ZAP70表达量与间变性胶质细胞瘤患者生存时间以及临床特征的关系,利用免疫组织化学染色验证ZAP70在临床间变性胶质细胞瘤样本中的表达量与患者预后的关系。通过GSEA(Gene Set Enrichment Analysis)富集分析了解ZAP70在间变性胶质细胞瘤中的相关功能通路。结果TCGA数据库中236例间变性胶质细胞瘤样本被分为低、中、高3个免疫浸润组,低免疫浸润组的预后最佳,中免疫浸润组次之,高免疫浸润组的预后最差。差异分析与单因素Cox回归分析筛选出ZAP70为间变性胶质细胞瘤免疫浸润相关的核心基因。K-M生存曲线显示,ZAP70高表达间变性胶质细胞瘤患者生存时间显著少于ZAP70低表达患者(P<0.05)。高表达ZAP70与多种不良的临床特征相关。61例临床间变性胶质细胞瘤样本的免疫组化染色分析验证了高表达ZAP70预后不佳的趋势。GSEA富集分析结果显示高表达ZAP70与耐药、细胞粘附、细胞外基质反应及恶性通路激活相关。在肿瘤免疫方面,ZAP70与白细胞迁移及固有免疫缺失相关。结论ZAP70有望成为间变性胶质细胞瘤患者中预后不佳亚群的诊断标记物及有效治疗靶点。展开更多
To the Editor:The z-chain-associated protein tyrosine kinase 70 kDa(ZAP70)deficiency is a rare autosomal recessive primary immunodeficiency characterized by absent CD8+T cells and non-functional CD4+T cells.[1]Accordi...To the Editor:The z-chain-associated protein tyrosine kinase 70 kDa(ZAP70)deficiency is a rare autosomal recessive primary immunodeficiency characterized by absent CD8+T cells and non-functional CD4+T cells.[1]According to current reports,approximately 18 pathogenic ZAP70 mutations have been identified in less than 30 patients.[1-4]ZAP70 deficiency always results in recurrent bacterial,viral,and opportunistic infections,diarrhea,and autoimmune diseases.Distinctively,ZAP70 hypomorphic mutations appear to have observable clinical heterogeneity,such as Epstein-Barr virus-associated lymphoproliferative disorder/lymphoma,late-onset immunodeficiency,[3]and silent brain infarcts.[5]Hence,next-generation sequencing technology might be the predominant diagnostic approach.展开更多
文摘目的探索间变性胶质细胞瘤中有预后价值的免疫浸润相关基因。方法下载TCGA(The Cancer Genome Atlas)数据库中转录组数据,量化间变性胶质细胞瘤样本的免疫浸润情况,并分为低、中、高免疫浸润组,进而对组间的差异基因进行分析,筛选出预后相关的核心基因ZAP70。研究ZAP70表达量与间变性胶质细胞瘤患者生存时间以及临床特征的关系,利用免疫组织化学染色验证ZAP70在临床间变性胶质细胞瘤样本中的表达量与患者预后的关系。通过GSEA(Gene Set Enrichment Analysis)富集分析了解ZAP70在间变性胶质细胞瘤中的相关功能通路。结果TCGA数据库中236例间变性胶质细胞瘤样本被分为低、中、高3个免疫浸润组,低免疫浸润组的预后最佳,中免疫浸润组次之,高免疫浸润组的预后最差。差异分析与单因素Cox回归分析筛选出ZAP70为间变性胶质细胞瘤免疫浸润相关的核心基因。K-M生存曲线显示,ZAP70高表达间变性胶质细胞瘤患者生存时间显著少于ZAP70低表达患者(P<0.05)。高表达ZAP70与多种不良的临床特征相关。61例临床间变性胶质细胞瘤样本的免疫组化染色分析验证了高表达ZAP70预后不佳的趋势。GSEA富集分析结果显示高表达ZAP70与耐药、细胞粘附、细胞外基质反应及恶性通路激活相关。在肿瘤免疫方面,ZAP70与白细胞迁移及固有免疫缺失相关。结论ZAP70有望成为间变性胶质细胞瘤患者中预后不佳亚群的诊断标记物及有效治疗靶点。
基金This work was supported by a grant from the National Natural Science Foundation of China(No.81871303).
文摘To the Editor:The z-chain-associated protein tyrosine kinase 70 kDa(ZAP70)deficiency is a rare autosomal recessive primary immunodeficiency characterized by absent CD8+T cells and non-functional CD4+T cells.[1]According to current reports,approximately 18 pathogenic ZAP70 mutations have been identified in less than 30 patients.[1-4]ZAP70 deficiency always results in recurrent bacterial,viral,and opportunistic infections,diarrhea,and autoimmune diseases.Distinctively,ZAP70 hypomorphic mutations appear to have observable clinical heterogeneity,such as Epstein-Barr virus-associated lymphoproliferative disorder/lymphoma,late-onset immunodeficiency,[3]and silent brain infarcts.[5]Hence,next-generation sequencing technology might be the predominant diagnostic approach.
