TY - JOUR T1 - Hub genes associated with immune cell infiltration in breast cancer, identified through bioinformatic analyses of multiple datasets JF - Cancer Biology & Medicine JO - Cancer Biology & Medicine SP - 1352 LP - 1374 DO - 10.20892/j.issn.2095-3941.2021.0586 VL - 19 IS - 9 AU - Huanyu Zhao AU - Ruoyu Dang AU - Yipan Zhu AU - Baijian Qu AU - Yasra Sayyed AU - Ying Wen AU - Xicheng Liu AU - Jianping Lin AU - Luyuan Li Y1 - 2022/09/15 UR - http://www.cancerbiomed.org/content/19/9/1352.abstract N2 - Objective: The aim of this study was to identify hub genes associated with immune cell infiltration in breast cancer through bioinformatic analyses of multiple datasets.Methods: Nonparametric (NOISeq) and robust rank aggregation-ranked parametric (EdgeR) methods were used to assess robust differentially expressed genes across multiple datasets. Protein-protein interaction network, GO, KEGG enrichment, and sub-network analyses were performed to identify immune-associated hub genes in breast cancer. Immune cell infiltration was evaluated with the CIBERSORT, XCELL, and TIMER methods. The association between the hub gene-based risk signature and survival was determined through Kaplan–Meier survival analysis, multivariate Cox analysis, and a nomogram with external verification.Results: We identified 163 robust differentially expressed genes in breast cancer through applying both nonparametric and parametric methods to multiple GEO (n = 2,212) and TCGA (n = 1,045) datasets. Integrated bioinformatic analyses further identified 10 hub genes: CXCL10, CXCL9, CXCL11, SPP1, POSTN, MMP9, DPT, COL1A1, ADAMDEC1, and RGS1. The 10 hub-gene-based risk signature significantly correlated with the prognosis of patients with breast cancer. Moreover, these hub genes were strongly associated with the extent of infiltration of CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and myeloid dendritic cells into breast tumors.Conclusions: Integrated analyses of multiple databases led to the discovery of 10 robust hub genes that together may serve as a risk factor characteristic of the immune microenvironment in breast cancer. ER -