Abstract：
BACKGROUND: NR4A family genes play crucial roles in cancers. However, the role of NR4A family genes in cancers remains paradoxical as they promote or suppress tumorigenesis.
OBJECTIVE: We aimed to conduct comprehensive analyses of the association between the expression of NR4A family genes and tumor microenvironment (TME) based on bioinformatics methods.
METHODS: We collected RNA-seq data from 33 cancer types and 20 normal tissue sites from the TCGA and GTEx databases. Expression patterns of NR4A family genes and their associations with DNA methylation, miRNA, overall survival, drug responses, and tumor microenvironment were investigated.
RESULTS: Significant downregulation of all NR4A family genes was observed in 15 cancer types. DNA promoter methylation and expression of NR4A family genes were negatively correlated in five cancers. The expression of 10 miRNAs targeting NR4A family genes was negatively correlated with the expression of NR4A family genes. High expression of all NR4A family genes was associated with poor prognosis in stomach adenocarcinoma and increased expressions of NR4A2 and NR4A3 were associated with poor prognosis in adrenocortical carcinoma. In addition, we found an elevated expression of NR4A2, which enhances the response to various chemotherapeutic drugs, whereas NR4A3 decreases drug sensitivity. Interestingly, in breast cancer, NR4A3 was significantly associated with C2 (IFN-γ dominant), C3 (inflammatory), and C6 (TGF-β dominant) immune subtypes and infiltrated immune cell types, implying both oncogenic and tumor-suppressive functions of NR4A3 in breast cancer.
CONCLUSIONS: The NR4A family genes have the potential to serve as a diagnostic, prognostic, and immunological marker of human cancers.
OBJECTIVE: We aimed to conduct comprehensive analyses of the association between the expression of NR4A family genes and tumor microenvironment (TME) based on bioinformatics methods.
METHODS: We collected RNA-seq data from 33 cancer types and 20 normal tissue sites from the TCGA and GTEx databases. Expression patterns of NR4A family genes and their associations with DNA methylation, miRNA, overall survival, drug responses, and tumor microenvironment were investigated.
RESULTS: Significant downregulation of all NR4A family genes was observed in 15 cancer types. DNA promoter methylation and expression of NR4A family genes were negatively correlated in five cancers. The expression of 10 miRNAs targeting NR4A family genes was negatively correlated with the expression of NR4A family genes. High expression of all NR4A family genes was associated with poor prognosis in stomach adenocarcinoma and increased expressions of NR4A2 and NR4A3 were associated with poor prognosis in adrenocortical carcinoma. In addition, we found an elevated expression of NR4A2, which enhances the response to various chemotherapeutic drugs, whereas NR4A3 decreases drug sensitivity. Interestingly, in breast cancer, NR4A3 was significantly associated with C2 (IFN-γ dominant), C3 (inflammatory), and C6 (TGF-β dominant) immune subtypes and infiltrated immune cell types, implying both oncogenic and tumor-suppressive functions of NR4A3 in breast cancer.
CONCLUSIONS: The NR4A family genes have the potential to serve as a diagnostic, prognostic, and immunological marker of human cancers.
摘要：
背景：NR4A家族基因在癌症中起着至关重要的作用。然而,NR4A家族基因在癌症中的作用仍然自相矛盾,因为它们促进或抑制肿瘤发生.
目的：我们旨在基于生物信息学方法对NR4A家族基因的表达与肿瘤微环境（TME）之间的关系进行综合分析。
方法：我们从TCGA和GTEx数据库中收集了33种癌症类型和20个正常组织部位的RNA-seq数据。NR4A家族基因的表达模式及其与DNA甲基化的关联,miRNA,总生存率,药物反应,并对肿瘤微环境进行了研究。
结果：在15种癌症类型中观察到所有NR4A家族基因的显著下调。5种癌症中DNA启动子甲基化与NR4A家族基因表达呈负相关。针对NR4A家族基因的10个miRNAs的表达与NR4A家族基因的表达呈负相关。所有NR4A家族基因的高表达与胃腺癌的不良预后有关，而NR4A2和NR4A3的高表达与肾上腺皮质癌的不良预后有关。此外,我们发现NR4A2的表达升高，这增强了对各种化疗药物的反应，而NR4A3降低药物敏感性。有趣的是,在乳腺癌中，NR4A3与C2（IFN-γ显性）显著相关，C3（炎症），和C6（TGF-β显性）免疫亚型和浸润免疫细胞类型，暗示NR4A3在乳腺癌中具有致癌和抑瘤功能。
结论：NR4A家族基因有潜力作为诊断，预后，和人类癌症的免疫标记。
目的：我们旨在基于生物信息学方法对NR4A家族基因的表达与肿瘤微环境（TME）之间的关系进行综合分析。
方法：我们从TCGA和GTEx数据库中收集了33种癌症类型和20个正常组织部位的RNA-seq数据。NR4A家族基因的表达模式及其与DNA甲基化的关联,miRNA,总生存率,药物反应,并对肿瘤微环境进行了研究。
结果：在15种癌症类型中观察到所有NR4A家族基因的显著下调。5种癌症中DNA启动子甲基化与NR4A家族基因表达呈负相关。针对NR4A家族基因的10个miRNAs的表达与NR4A家族基因的表达呈负相关。所有NR4A家族基因的高表达与胃腺癌的不良预后有关，而NR4A2和NR4A3的高表达与肾上腺皮质癌的不良预后有关。此外,我们发现NR4A2的表达升高，这增强了对各种化疗药物的反应，而NR4A3降低药物敏感性。有趣的是,在乳腺癌中，NR4A3与C2（IFN-γ显性）显著相关，C3（炎症），和C6（TGF-β显性）免疫亚型和浸润免疫细胞类型，暗示NR4A3在乳腺癌中具有致癌和抑瘤功能。
结论：NR4A家族基因有潜力作为诊断，预后，和人类癌症的免疫标记。
