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作为乳腺癌的免疫相关生物标志物:一项基于多个数据库的研究。

as an Immune-Related Biomarker for Breast Cancer: A Study Based on Multiple Databases.

机构信息

Central Laboratory of the Fifth Affiliated Hospital of Harbin Medical University, Daqing 163711, Heilongjian Province, China.

Clinical Laboratory of the Fifth Affiliated Hospital of Harbin Medical University, Daqing 163316, Heilongjian Province, China.

出版信息

Chin Med Sci J. 2024 Sep 30;39(3):171-181. doi: 10.24920/004340.

Abstract

OBJECTIVES

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 in BRCA were explored using R language, TIMER, and Gene Set Enrichment Analysis (GSEA).

RESULTS

Of 10 hub genes seleceed from 302 DEGS, was identified as the gene associated with BRCA survival. The expression of was differentially upregulated in BRCA, as verified by TCGA and qRT-PCR. Prognostic analysis revealed that served as an independent prognostic factor. High expression of 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 in BRCA showed a significant correlation with immune checkpoints genes , , and expressions. There was a positive correlation between the expression of and the tumor mutational burden and microsatellite instability. GSEA demonstrated that expression significantly enriched 786 immune-related gene sets.

CONCLUSIONS

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. may be an potential immune-related prognostic biomarker for BRCA.

摘要

目的

利用多个数据库筛选与乳腺癌(BRCA)生存相关的靶基因,并探讨其预后价值及与 BRCA 的免疫相关性。

方法

从基因表达综合数据库(GEO)中下载 BRCA 的微阵列表达数据集,进行分析以获得差异表达基因(DEGs)。通过构建和可视化 DEGs 的蛋白质-蛋白质相互作用网络,获得枢纽基因。使用 R 语言、STRING 和 Cytoscape 确定关键基因,并使用外部数据集 The Cancer Genome Atlas(TCGA)和 37 例 BRCA 组织的定量实时 PCR(qRT-PCR)验证关键基因的差异表达。使用 R 语言、TIMER 和基因集富集分析(GSEA)探索在 BRCA 中的预后价值和免疫相关性。

结果

从 302 个 DEGs 中选择了 10 个枢纽基因,其中 被鉴定为与 BRCA 生存相关的基因。TCGA 和 qRT-PCR 验证了 BRCA 中 的表达差异上调。预后分析表明, 是独立的预后因素。BRCA 组织中 高表达与 B 细胞、CD4+T 细胞、CD8+T 细胞、巨噬细胞和髓样树突状细胞的免疫浸润水平降低有关。BRCA 中 的表达与免疫检查点基因 、 、 的表达呈显著相关。 与肿瘤突变负荷和微卫星不稳定性呈正相关。GSEA 表明, 表达显著富集了 786 个免疫相关基因集。

结论

BRCA 组织中 的表达与 BRCA 免疫微环境密切相关,对 BRCA 患者的生存和预后及免疫治疗效果具有预测价值。 可能是 BRCA 的潜在免疫相关预后生物标志物。

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