目的 利用多种基因表达数据库和公共生物信息学平台，分析出与乳腺癌预后和免疫相关的关键基因，并对关键基因在乳腺癌中的预后价值和免疫作用情况进行验证和探讨。方法 从Gene Expression Omnibus(GEO)数据库下载乳腺癌基因芯片表达数据集，分析获得差异表达基因(differentially expressed genes，DEGs)。通过构建和可视化DEGs-蛋白相互作用网络获得枢纽基因，利用R语言、STRING和Cytoscape等工具在枢纽基因中确定关键基因，利用外部数据集和The Cancer Genome Atlas(TCGA)验证关键基因差异表达情况，利用定量实时聚合酶链式反应(quantitative real-time polymerase chain reaction，qRT-PCR)验证关键基因在37个乳腺癌组织和相对应的癌旁组织中的差异表达情况，使用R语言、TIMER和Gene Set Enrichment Analysis(GSEA)等生物信息学工具和平台研究关键基因在乳腺癌中的预后价值和免疫学相关性。结果 率先从302个差异基因中获取了10个枢纽基因，并通过生存分析筛选出关键基因UBE2C。GEO独立数据集、TCGA和qRT-PCR均证实UBE2C在乳腺癌组织中差异上调。预后分析显示UBE2C是一个独立的预后因素。UBE2C高表达降低乳腺癌组织中B细胞、CD4+T细胞、CD8+T细胞、巨噬细胞和髓系树突状细胞免疫浸润水平。UBE2C在乳腺癌中的表达与免疫检查点基因PDCD1、CD274和CTLA4的表达显著相关。UBE2C的表达与肿瘤突变负荷水平和微卫星不稳定性水平呈显著正相关。GSEA分析显示，在786个免疫相关基因集中UBE2C表达显著富集。结论 UBE2C在乳腺癌组织中的表达与乳腺癌免疫微环境密切相关，其表达情况对预测乳腺癌患者的生存、预后和免疫治疗效果具有一定价值。UBE2C是乳腺癌的一种潜在的免疫相关的预后生物标志物。
UBE2C as an Immune-Related Biomarker for Breast Cancer:A Study Based on Multiple Databases
Objective To screen the target genes that are associated with survival of breast cancer(BRCA)and explore their prognostic values and immune correlations with BRCA using multiple databases..Methods The microarray expression datasets of BRCA were downloaded from the Gene Expresssion Omnibus database(GEO)and analyzed to obtain differentially expressed genes(DEGs).Hub genes were obtained by constructing and visualizing the protein-protein interaction network of DEGs.The key gene was determined using R language,STRING,and Cytoscape,and the differential expression of the key gene was verified using external datasets The Cancer Genome Atlas(TCGA)and quantitative real-time PCR(qRT-PCR)for BRCA tissues of 37 patients.The prognostic value and immunological correlation of UBE2C in BRCA were explored using R language,TIMER,and Gene Set Enrichment Analysis(GSEA).Results Of 10 hub genes seleceed from 302 DEGS,UBE2C was identified as the gene associated with BRCA survival.The expression of UBE2C was differentially upregulated in BRCA,as verified by TCGA and qRT-PCR.Prognostic analysis revealed that UBE2C served as an independent prognostic factor.High expression of UBE2C was associated with decreased immune infiltration levels of B cells,CD4+T cells,CD8+T cells,macrophages,and myeloid dendritic cells in BRCA tissue.The expression of UBE2C in BRCA showed a significant correlation with immune checkpoints genes PDCD1,CD274,and CTLA4 expressions.There was a positive correlation between the expression of UBE2C and the tumor mutational burden and microsatellite instability.GSEA demonstrated that UBE2C expression significantly enriched 786 immune-related gene sets.Conclusions UBE2C expression in BRCA tissues is closely related to the BRCA immune microenvironment and showes predictive values on the survivals and prognosis of BRCA patients and the effecacy of immunotherapy.UBE2C may be an potential immune-related prognostic biomarker for BRCA.
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