在乳腺癌免疫微环境中的作用。

The Role of in the Immune Microenvironment of Breast Cancer.

机构信息

Department of General Surgery, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, 224005 Yancheng, Jiangsu, China.

出版信息

Front Biosci (Landmark Ed). 2024 Feb 21;29(2):73. doi: 10.31083/j.fbl2902073.

DOI:10.31083/j.fbl2902073

PMID:38420798

Abstract

BACKGROUND

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer (BC), and it is often associated with a high tumor grade, a younger age at diagnosis, and a low survival rate. Conventional endocrine and anti-HER-2 therapies are usually ineffective against TNBC, creating treatment challenges and resulting in a poor prognosis. Hence, new targets and treatment strategies for TNBC are urgently required.

METHODS

The GSE102818 dataset was used to identify differentially expressed genes (DEGs) between primary BC and metastatic BC lesions. The Cancer Genome Atlas and the cBioPortal platform were employed to explore mutations in candidate genes. Utilizing the Tumor IMmune Estimation Resource (TIMER), the relationship between the expression of candidate genes and immune cell infiltration was assessed. Additionally, the cell-specific expression of the candidate genes was examined in the immune microenvironment of primary BC and metastatic BC lesions using the single-cell RNA sequencing (scRNA-seq) datasets GSE118389 and GSE202695. Finally, the protein expression of the candidate genes in clinical TNBC samples was evaluated.

RESULTS

was identified as a hub gene in the DEG network and was found to be down-regulated in metastatic BC lesions. expression was highly correlated with the infiltration of CD8+ T cells, and elevated expression was correlated with improved survival. Interestingly, scRNA-seq data revealed that was down-regulated in CD8+ T cells in the immune microenvironment of metastatic BC lesions. Finally, the evaluation of clinical samples confirmed the down-regulation of in the immune microenvironment of BC lung metastases.

CONCLUSIONS

In patients with metastatic TNBC, high levels of (especially in the immune microenvironment) are associated with a good prognosis.

摘要

背景

三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌（BC），常与高肿瘤分级、诊断时年龄较小和低生存率相关。常规的内分泌和抗 HER-2 治疗通常对 TNBC 无效，这给治疗带来了挑战，导致预后较差。因此，迫切需要针对 TNBC 的新靶点和治疗策略。

方法

使用 GSE102818 数据集鉴定原发性 BC 和转移性 BC 病变之间的差异表达基因（DEGs）。利用癌症基因组图谱和 cBioPortal 平台探索候选基因的突变。利用肿瘤免疫估计资源（TIMER）评估候选基因表达与免疫细胞浸润的关系。此外，使用单细胞 RNA 测序（scRNA-seq）数据集 GSE118389 和 GSE202695，在原发性 BC 和转移性 BC 病变的免疫微环境中检查候选基因的细胞特异性表达。最后，评估候选基因在临床 TNBC 样本中的蛋白表达。