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

Abstract

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. 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. 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. 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.