基于生物信息学分析鉴定乳腺癌微环境中具有预后价值的基因。

Identification of Genes with Prognostic Value in the Breast Cancer Microenvironment Using Bioinformatics Analysis.

机构信息

Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland).

Department of Urology Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland).

出版信息

Med Sci Monit. 2020 Apr 6;26:e920212. doi: 10.12659/MSM.920212.

Abstract

BACKGROUND Stromal and immune cells play essential roles in the development of breast cancer (BC). This study was conducted to identify prognosis-related genes from the tumor microenvironment. MATERIAL AND METHODS The gene expression profiles of 622 BC samples were downloaded from TCGA (The Cancer Genome Atlas) database. Stromal and immune scores were calculated by using the ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumours using Expression data) algorithm. Then, differentially expressed genes (DEGs) between the high score group and the low score group were screened. The intersecting DEGs were selected through Venn diagrams, and survival analysis was conducted. Functional and pathway enrichment analyses were performed using the DAVID (Database for Annotation, Visualization and Integrated Discovery), and a protein-protein interaction (PPI) network was constructed with the STRING database and Cytoscape. These genes were validated for prognostic value by use of the KM (Kaplan-Meier) plotter tool. RESULTS The low immune score group was associated with a poor prognosis. However, there was no difference in the prognosis between the high and low stromal score groups. A total of 248 intersecting DEGs were found in BC, and 61 genes were significantly associated with the prognosis of BC patients in the TCGA database. These genes were enriched in the immune response, components of the plasma membrane, and receptor activity. Furthermore, in the validation group, 31 of 61 genes were significantly associated with prognosis. CONCLUSIONS Our bioinformatics analysis identified 31 tumor microenvironment-related genes as potential prognostic predictors for breast cancer patients. Some of these genes that have not been widely investigated previously, such as CXCL9, GPR18, S1PR4, SASH3, and PYH1N1, might be additional predictive factors for BC patients.

摘要

背景

基质和免疫细胞在乳腺癌(BC)的发展中起着至关重要的作用。本研究旨在从肿瘤微环境中鉴定与预后相关的基因。

材料和方法

从 TCGA(癌症基因组图谱)数据库下载了 622 例 BC 样本的基因表达谱。使用 ESTIMATE(基于表达数据估计恶性肿瘤中的基质和免疫细胞)算法计算基质和免疫评分。然后筛选高评分组和低评分组之间的差异表达基因(DEGs)。通过 Venn 图选择交迭的 DEGs,并进行生存分析。使用 DAVID(数据库注释、可视化和综合发现)进行功能和通路富集分析,并使用 STRING 数据库和 Cytoscape 构建蛋白质-蛋白质相互作用(PPI)网络。使用 KM(Kaplan-Meier)绘图器工具验证这些基因的预后价值。

结果

低免疫评分组与预后不良相关。然而,高和低基质评分组之间的预后没有差异。在 BC 中发现了 248 个交迭的 DEGs,在 TCGA 数据库中,有 61 个基因与 BC 患者的预后显著相关。这些基因富集在免疫反应、质膜成分和受体活性中。此外,在验证组中,有 31 个基因与预后显著相关。

结论

我们的生物信息学分析确定了 31 个肿瘤微环境相关基因作为乳腺癌患者潜在的预后预测因子。其中一些以前没有广泛研究过的基因,如 CXCL9、GPR18、S1PR4、SASH3 和 PYH1N1,可能是 BC 患者的额外预测因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/548c/7160604/989fcf1cc112/medscimonit-26-e920212-g001.jpg

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