摘要
目的探讨坏死性凋亡基因核苷酸结合寡聚化结构域2(NOD2)在睾丸癌(TGCT)中的预后意义,并分析其与睾丸癌肿瘤免疫调控的相关性。方法本研究于2024年10月至2024年12月期间,使用肿瘤基因组图谱(TCGA)数据库中的TGCT患者数据,通过R包"TCGAbiolinks"获取患者临床信息和转录组表达数据。筛选出与坏死性凋亡相关的756个基因,通过Cox回归分析和LASSO筛选方法确定NOD2为关键基因,并分析其与基因突变之间的关系。同时,采用6种免疫评分方法(CIBERSORT、EPIC、MCPCOUNTER、QUANTISEQ、TIMER、XCELL)评估NOD2表达与免疫细胞浸润的Spearman相关性。结果共筛选出10个与TGCT患者生存预后显著相关的坏死性凋亡基因,其中SRP14表达与生存预后呈负相关(HR=0.723,P<0.01);TLR4、NINJ1、MEFV、TNFSF10、NLRP3、GNLY、NOD2、LITAF和KRT9(HR=1.475、1.329、1.418、1.536、1.613、1.592、1.782、1.433、1.544,P<0.05)表达与生存预后呈正相关。NOD2高表达组中,KIT基因突变频率高达34.4%。免疫浸润分析表明,NOD2与CD8+T细胞(R=0.52,P<0.01,EPIC算法)、CD4+T细胞(R=0.49,P<0.01,EPIC算法)以及巨噬细胞(R=0.48,P<0.01,TIMER算法)浸润呈显著正相关。结论NOD2在TGCT中的高表达与生存预后、基因突变及免疫浸润密切相关,NOD2可能通过调控免疫逃逸和免疫微环境参与TGCT的发生和发展。
Objective To explore the prognostic significance of the necroptosis-related gene nucleotide-binding oligomerization domain-containing protein 2(NOD2)in testicular germ cell tumors(TGCT),and to analyze its relationship with immune infiltration and gene mutations.Methods This study used the TGCT patient data from the TCGA database from October 2024 to December 2024.The case and transcriptome expression data were obtained through the R package"TCGAbiolinks".Firstly,756 genes related to necroptosis were screened out.The key genes related to survival were determined through Cox regression analysis and LASSO screening methods.Then,the expression differences of NOD2 were analyzed using Sangerbox and the Clinical Bioinformatics Home platform,and its relationship with gene mutations was analyzed.At the same time,six immune scoring methods(CIBERSORT,EPIC,MCPCOUNTER,QUANTISEQ,TIMER,XCELL)were used to evaluate the Spearman correlation between NOD2 expression and immune cell infiltration.A P value<0.05 was considered statistically significant.Results A total of 10 necroptosis-related genes significantly associated with prognosis in TGCT patients were identified.Among them,SRP14 expression was negatively correlated with prognosis(HR=0.723,P<0.01),while TLR4,NINJ1,MEFV,TNFSF10,NLRP3,GNLY,NOD2 LITAF,and KRT9(HR=1.475,1.329,1.418,1.536,1.613,1.592,1.782,1.433,1.544,P<0.05)expression levels were positively correlated.In the high NOD2 expression group,the mutation frequency of the KIT gene reached up to 34.4%.Immune infiltration analysis demonstrated significant positive correlations between NOD2 expression and infiltration of CD8+T cells(R=0.52,P<0.01,EPIC algorithm),CD4+T cells(R=0.49,P<0.01,EPIC algorithm),and macrophages(R=0.48,P<0.01,TIMER algorithm).Conclusion The high expression of NOD2 in TGCT is closely related to survival prognosis,gene mutations,and immune infiltration.NOD2 may participate in the occurrence and development of TGCT by regulating immune escape and immune microenvironment.
作者
兰东阳
安韶光
李志愿
兀戈平
陈尚
杜秋争
高宇奎
闫泽晨
Lan Dongyang;An Shaoguang;Li Zhiyuan;Wu Geping;Chen Shang;Du Qiuzheng;Gao Yukui;Yan Zechen(Department of Urology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Institute of Molecular Oncology,Zhengzhou University,Zhengzhou 450052,China;Department of Urology,Yijishan Hospital of Anhui Nanmin Medical University,Wuhu 241001,China)
出处
《中华实验外科杂志》
2025年第4期679-682,共4页
Chinese Journal of Experimental Surgery
基金
河南省医学科技攻关项目(SBGJ202402052)
郑州大学青年骨干教师(2023ZDGGJS083)。
关键词
生物信息学
核苷酸结合寡聚化结构域2
免疫浸润
睾丸癌
Bioinformatics
Nucleotide Binding oligomerization domain 2
Immune infiltration
Testicular cancer
