Identification of T cell-related biomarkers for breast cancer based on weighted gene co-expression network analysis.

ABSTRACT

Breast cancer is the most frequent malignancy worldwide, with immunotherapy and targeted therapy being key strategies to improving the prognosis. We downloaded mRNA expression dataset of breast cancer from The Cancer Genome Atlas (TCGA) database, and divided preprocessed genes into 12 modules based on gene expression profile by weighted gene co-expression network analysis (WGCNA). The StromalScore, ImmuneScore and ESTIMATEScore of samples were assessed. The Kaplan-Meier curve showed that ImmuneScore was notably correlated with breast cancer patient's prognosis. By analyzing the connectivity between module eigengenes and clinical traits, the gene module closely related to ImmuneScore was obtained. Further, through intramodular gene connectivity and protein-protein interaction network topology analysis of module genes, hub genes (HLA-E, HLA-DPB1 and HLA-DRB1) in immune-related module were screened out. Finally, bioinformatics analysis displayed that HLA-DPB1 and HLA-DRB1 were notably overexpressed and HLA-E was underexpressed in breast cancer tissues. TIMER database analysis showed that three hub gene levels were significantly correlated with infiltration levels of CD8+ T cells and CD4+ T cells. Meanwhile, Pearson correlation analysis revealed positive correlation between three hub genes and those of immune checkpoint genes (LAG3, PD-1, PD-L1). Additionally, prognosis could be effectively evaluated by HLA-DPB1 and HLA-DRB1 levels, and differentially activated signalling pathways between high- and low-expression groups of HLA-E and HLA-DPB1 were obtained by gene set enrichment analysis. To conclude, this study identified three T cell-related biomarkers for breast cancer based on TCGA-BRCA dataset, and the screened genes could provide references for breast cancer immunotherapy.