建立一种用于区分和预测三阴性乳腺癌预后的新型细胞因子相关8基因特征。

Establishment of a novel cytokine-related 8-gene signature for distinguishing and predicting the prognosis of triple-negative breast cancer.

作者信息

Liu Xiaojun, Zhang Liang, Chen Liang

机构信息

Second Department of Nail and Breast Surgery, Cangzhou Central Hospital, Cangzhou, China.

出版信息

Front Med (Lausanne). 2023 Jun 2;10:1189361. doi: 10.3389/fmed.2023.1189361. eCollection 2023.

DOI:10.3389/fmed.2023.1189361

PMID:37332770

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10275569/

Abstract

BACKGROUND

Triple-negative breast cancer (TNBC) is a common carcinoma in women, and the prognosis of TNBC is the worst. Using data from The Cancer Genome Atlas (TCGA) database, we analyzed the functional roles of cytokine-related genes in TNBC.

METHODS

The clinical and transcriptome data of TNBC patients were downloaded from TCGA database. A systematical analyses of the data from TCGA database were conducted to screen the prognostic genes and identify the main cytokine-related pathways related to TNBC.

RESULTS

We identified 499 prognostic genes in TNBC patients from TCGA database and the cytokine-related pathways closely related to TNBC. TCGA-TNBC patients were divided into the high-risk cluster (C1) group and the low-risk cluster (C2) group based on the cytokine-related genes. The C1 group patients exhibited tumor metastasis and an advanced tumor stage. The functional analysis revealed that the upregulated differentially expressed genes (DEGs) in the C1 group were mainly associated with the extracellular matrix (ECM)-receptor interaction, stem cell proliferation, focal adhesion, and cyclic adenosine monophosphate (cAMP) signaling pathway, while the downregulated DEGs in the C1 group were mainly associated with cytokine and cytokine receptors, T-helper 17 (Th17) cell differentiation, and primary immunodeficiency. The immune activity of C1 group was lower than that of C2 group, and the identified half-maximal inhibitory concentration scores of 3 chemotherapy drugs (i.e., doxorubicin, methotrexate, and paclitaxel) were lower in C2 group than C1 group. More importantly, we constructed a novel prognostic signature and identified the following 8 genes: CCL25, CXCL13, IL12RB2, IL21, TNFRSF13C, TNFRSF8, CCL7 and GDF5.

CONCLUSION

The status of the cytokine-related pathway was closely related to tumor classification and immune activity in the TNBC patients. The gene signature of the cytokine-related genes showed an good performance in predicting the prognosis of TNBC patients, and could predict the prognosis of TNBC patients.

摘要

背景

三阴性乳腺癌（TNBC）是女性常见的癌症，其预后最差。利用癌症基因组图谱（TCGA）数据库的数据，我们分析了细胞因子相关基因在TNBC中的功能作用。

方法

从TCGA数据库下载TNBC患者的临床和转录组数据。对TCGA数据库的数据进行系统分析，以筛选预后基因并确定与TNBC相关的主要细胞因子相关通路。

结果

我们从TCGA数据库中确定了TNBC患者的499个预后基因以及与TNBC密切相关的细胞因子相关通路。基于细胞因子相关基因，将TCGA-TNBC患者分为高危聚类（C1）组和低危聚类（C2）组。C1组患者表现出肿瘤转移和肿瘤分期较晚。功能分析显示，C1组中上调的差异表达基因（DEG）主要与细胞外基质（ECM）-受体相互作用、干细胞增殖、粘着斑和环磷酸腺苷（cAMP）信号通路相关，而C1组中下调的DEG主要与细胞因子和细胞因子受体、辅助性T细胞17（Th17）细胞分化和原发性免疫缺陷相关。C1组的免疫活性低于C2组，并且在C2组中3种化疗药物（即阿霉素、甲氨蝶呤和紫杉醇）的半数最大抑制浓度得分低于C1组。更重要的是，我们构建了一种新的预后特征并确定了以下8个基因：CCL25、CXCL13、IL12RB2、IL21、TNFRSF13C、TNFRSF8、CCL7和GDF5。