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基于生物信息学筛选肉瘤免疫微环境中的预后标记物

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目的 基于生物信息学筛选肉瘤免疫微环境中的预后标记物,旨在为肉瘤免疫治疗方案制定提供参考。方法 下载癌症基因图谱(TCGA)数据库中 265 个肉瘤的RNA-seq表达谱。利用R语言"limma"包筛选差异表达基因(DEGs),Veen图获取共同的DEGs。利用蛋白质-蛋白质互相作用(PPI)网络互作分析结合Cytoscape软件获取关键的DEGs;利用GEPIA数据库鉴定预后的相关基因,TIMER数据库中分析基因表达与免疫细胞浸润水平的相关性;基因富集分析(GSEA)验证关键基因对免疫相关信号通路调节作用。结果 Kaplan-Meier生存分析结果表明,Immune Score、Stromal Score和ESTIMATE Score与肉瘤患者总生存时间(OS)和疾病特异性生存时间(DSS)呈正相关(P<0。05)。PPI核心模块中主要包含了 10 个核心的基因,即CD4、LCK、PTPN6、SYK、CD8A、PTPRC、CD3D、CD3E、LCP2、ITGAM,其中LCK、CD3E、PTPN6 关键基因与患者的不良预后和免疫细胞浸润水平显著相关。单基因GSEA分析表明,LCK、CD3E及PTPN6 表达上调能够显著地富集在T细胞受体信号通路。结论 LCK、CD3E及PTPN6 表达与肉瘤患者的预后和免疫细胞浸润有关,这一发现可能有助于改进肉瘤患者的免疫治疗。
Screening prognostic markers in the immune microenvironment of sarcoma based on bioinformatics
Objective To screen prognostic markers in the immune microenvironment of sarcoma based on bioinformatics,and to provide a reference for the development of sarcoma immunotherapy regimens.Methods The RNA-seq expression profiles of 265 sarcomas in the Cancer Genome Atlas(TCGA)database were downloaded.Differentially expressed genes(DEGs)were screened by R language"limma"package,and common DEGs were obtained by Veen plot.Protein-protein interactions(PPI)network interaction analysis combined with Cytoscape software was used to obtain key DEGs.The GEPIA database was used to identify prognostic genes,and the correlation between gene expression and immune cell infiltration level was analyzed by TIMER database.Gene set enrichment analysis(GSEA)was used to verify the regulation of key genes on immune-related signaling pathways.Results Kaplan-Meier survival analysis results showed that Immune Score,Stromal Score and ESTIMATE Score were positively correlated with overall survival(OS)and disease specific survival(DSS)in patients with sarcoma(P<0.05).The PPI core module mainly contained 10 core genes,namely CD4,LCK,PTPN6,SYK,CD8A,PTPRC,CD3D,CD3E,LCP2 and ITGAM.The key genes of LCK,CD3E and PTPN6 were significantly related to the poor prognosis and immune cell infiltration level of patients.Single gene GSEA analysis showed that the up-regulated expression of LCK,CD3E and PTPN6 could be significantly enriched in the T cell receptor signaling pathway.Conclusion The expression of LCK,CD3E and PTPN6 is related to the prognosis and immune cell infiltration of sarcoma patients.This finding may help to improve the immunotherapy of sarcoma patients.

sarcomabioinformaticsimmune microenvironmentimmune cell infiltrationprognosis

王延峰、王虎霞、宋张骏

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西安交通大学医学部,陕西 西安,710061

陕西省人民医院乳腺科,陕西 西安,710068

延安大学附属医院检验科,陕西 延安,716000

陕西省肿瘤医院乳腺科,陕西 西安,710000

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肉瘤 生物信息学 免疫微环境 免疫细胞浸润 预后

陕西省自然科学基础研究计划项目陕西省感染与免疫疾病重点实验室开放课题项目陕西省人民医院2021年科技人才支持计划资助项目秦创原中医药创新研发转化项目

2022JZ-572022-ZD-22021LJ-012022-QCYZH-004

2024

临床医学研究与实践

临床医学研究与实践

ISSN:
年,卷(期):2024.9(7)
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