铁死亡相关基因DPP4与肿瘤免疫及预后的生物信息学研究  

Bioinformatics study on ferroptosis related gene DPP4 in tumor immunity and prognosis

作　　者：陈静 张尚暖(指导)[2] CHEN Jing;ZHANG Shangnuan(School of Clinical and Basic Medical Sciences,Shandong First Medical University,Shandong Academy of Medical Sciences,Jinan 250117,China)

机构地区：[1]山东第一医科大学,山东省医学科学院临床与基础医学院,济南250117 [2]济宁市第一人民医院,济宁272002

出　　处：《中国免疫学杂志》2023年第11期2348-2354,2360,共8页Chinese Journal of Immunology

基　　金：泰安市科技发展计划(引导计划)(2021NS261)资助。

摘　　要：目的:分析铁死亡相关基因DPP4在泛癌中的表达及其在肿瘤免疫、预后等方面的作用,探讨DPP4在肿瘤免疫治疗及临床预后中的价值。方法:利用CCLE、TCGA及GTEx数据库对铁死亡相关基因DPP4进行泛癌的差异表达分析,并通过Kaplan-Meier及Cox回归分析DPP4与肿瘤预后的相关性;使用CIBERSORT算法评估TIMER数据库中肿瘤免疫细胞浸润情况,ESTIMATE算法评估肿瘤微环境,Spearman检验分析基因表达与免疫新抗原、肿瘤突变负荷及微卫星不稳定性的关联;GSEA软件研究DPP4在肿瘤中的表达与信号通路的相关性。结合人类蛋白质图谱数据库、TCGA数据库及GEO数据库对分析结果进行验证。结果:DPP4基因在多种肿瘤中的表达差异具有统计学意义,且与多种肿瘤的生存及预后密切相关,其中在嗜铬细胞瘤和副神经节瘤(PCPG)、胸腺癌(THYM)中可作为保护因素,对肿瘤预后有正向作用;DPP4与肿瘤的多种免疫细胞浸润及免疫微环境密切相关,最显著相关的3类肿瘤为膀胱尿路上皮癌(BLCA)、乳腺浸润癌(BRCA)、嗜铬细胞瘤和副神经节瘤(PCPG);DPP4与免疫新抗原、肿瘤突变负荷与微卫星不稳定性显著相关;GSEA分析结果显示存在多个与DPP4在肿瘤中高低表达相关的生物学通路,主要集中于物质代谢及炎症反应等通路;人类蛋白质图谱和TCGA、GEO数据库证实DPP4在肺癌、乳腺癌、直肠癌和前列腺癌中表达存在差异。结论:铁死亡相关基因DPP4可作为肿瘤免疫治疗的生物靶点用于泛癌预后评估,对临床肿瘤诊断、治疗及预后具有重要意义。Objective:To explore value of DPP4 in tumor immunotherapy and clinical prognosis by analyzing expression of ferroptosis-related gene DPP4 in pan-cancer and its function in tumor immunity and prognosis.Methods:Differential expression of ferroptosis-related gene DPP4 was analyzed in pan-cancer by CCLE database,TCGA database and GTEx database,and correlation between DPP4 and tumor prognosis was analyzed by Kaplan-Meier and Cox regression;CIBERSORT algorithm was used to evaluate immune cells infiltration of tumors in TIMER database,ESTIMATE algorithm was used to evaluate tumor microenvironment,and Spearman test was used to analyze correlation between gene expression and immune neoantigens,tumor mutation burden and microsatellite instability;GSEA software was used to study expression of DPP4 in tumors correlation with signaling pathways.Analysis results were verified by human protein map database,TCGA database and GEO database.Results:Expression difference of DPP4 gene in various tumors was statistically significant,which was closely related to survival and prognosis of various tumors.Among them,DPP4 could be used as a significant protective factor and had a positive effect on tumor prognosis in PCPG and THYM;DPP4 was closely related to various immune cell infiltration and immune microenvironment of tumors,and three types of tumors,BLCA,BRCA and PCPG were most significantly related;DPP4 was significantly related to immune neoantigens,tumor mutation load and microsatellite instability;GSEA analysis results show that there were multiple biological pathways related to high and low expression of DPP4 in tumors,mainly in pathways of substance metabolism and inflammatory response.Human protein Atls,TCGA and GEO database showeel that there were differences in DPP4 expression among rectal and prostate cancers.Conclusion:Ferroptosis-related gene DPP4 can be used as a biological target of tumor immunotherapy for prognosis evaluation of pan-cancer,which is of great significance for diagnosis,treatment and prognosis of clinical t

关 键 词：铁死亡 DPP4 肿瘤 预后评估 免疫微环境 变异 

分 类 号：R737.1[医药卫生—肿瘤]