肿瘤微环境中具有预后价值的新型免疫相关基因在乳腺癌中的研究。
Novel immune-related genes in the tumor microenvironment with prognostic value in breast cancer.
机构信息
Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Department of General Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
出版信息
BMC Cancer. 2021 Feb 6;21(1):126. doi: 10.1186/s12885-021-07837-1.
BACKGROUND
Breast cancer is one of the most frequently diagnosed cancers among women worldwide. Alterations in the tumor microenvironment (TME) have been increasingly recognized as key in the development and progression of breast cancer in recent years. To deeply comprehend the gene expression profiling of the TME and identify immunological targets, as well as determine the relationship between gene expression and different prognoses is highly critical.
METHODS
The stromal/immune scores of breast cancer patients from The Cancer Genome Atlas (TCGA) were employed to comprehensively evaluate the TME. Then, TME characteristics were assessed, overlapping genes of the top 3 Gene Ontology (GO) terms and upregulated differentially expressed genes (DEGs) were analyzed. Finally, through combined analyses of overall survival, time-dependent receiver operating characteristic (ROC), and protein-protein interaction (PPI) network, novel immune related genes with good prognosis were screened and validated in both TCGA and GEO database.
RESULTS
Although the TME did not correlate with the stages of breast cancer, it was closely associated with the subtypes of breast cancer and gene mutations (CDH1, TP53 and PTEN), and had immunological characteristics. Based on GO functional enrichment analysis, the upregulated genes from the high vs low immune score groups were mainly involved in T cell activation, the external side of the plasma membrane, and receptor ligand activity. The top GO terms of the upregulated DEGs from the high vs low immune score groups exhibited better prognosis in breast cancer; 15 of them were related to good prognosis in breast cancer, especially CD226 and KLRC4-KLRK1.
CONCLUSIONS
High CD226 and KLRC4-KLRK1 expression levels were identified and validated to correlate with better overall survival in specific stages or subtypes of breast cancer. CD226, KLRC4-KLRK1 and other new targets seem to be promising avenues for promoting antitumor targeted immunotherapy in breast cancer.
背景
乳腺癌是全球女性中最常见的癌症之一。近年来，肿瘤微环境（TME）的改变被越来越多地认为是乳腺癌发生和发展的关键。深入了解 TME 的基因表达谱，识别免疫靶点，以及确定基因表达与不同预后之间的关系至关重要。
方法
我们利用癌症基因组图谱（TCGA）中乳腺癌患者的基质/免疫评分来全面评估 TME。然后，评估 TME 特征，分析前 3 个基因本体论（GO）术语的重叠基因和上调差异表达基因（DEGs）。最后，通过综合分析总生存期、时间依赖的接收器工作特征（ROC）和蛋白质-蛋白质相互作用（PPI）网络，在 TCGA 和 GEO 数据库中筛选和验证具有良好预后的新型免疫相关基因。
结果
尽管 TME 与乳腺癌的分期无关，但它与乳腺癌的亚型和基因突变（CDH1、TP53 和 PTEN）密切相关，并且具有免疫学特征。基于 GO 功能富集分析，高与低免疫评分组上调基因主要涉及 T 细胞激活、质膜外和受体配体活性。高与低免疫评分组上调 DEGs 的顶级 GO 术语在乳腺癌中表现出更好的预后；其中 15 个与乳腺癌的良好预后相关，特别是 CD226 和 KLRC4-KLRK1。
结论
高表达的 CD226 和 KLRC4-KLRK1 与特定阶段或亚型乳腺癌的总生存期延长相关。CD226、KLRC4-KLRK1 和其他新靶点似乎是促进乳腺癌抗肿瘤靶向免疫治疗的有前途的途径。
Zotero 插件