@article {Zhao1352, author = {Huanyu Zhao and Ruoyu Dang and Yipan Zhu and Baijian Qu and Yasra Sayyed and Ying Wen and Xicheng Liu and Jianping Lin and Luyuan Li}, title = {Hub genes associated with immune cell infiltration in breast cancer, identified through bioinformatic analyses of multiple datasets}, volume = {19}, number = {9}, pages = {1352--1374}, year = {2022}, doi = {10.20892/j.issn.2095-3941.2021.0586}, publisher = {Cancer Biology \& Medicine}, abstract = {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{\textendash}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.}, issn = {2095-3941}, URL = {https://www.cancerbiomed.org/content/19/9/1352}, eprint = {https://www.cancerbiomed.org/content/19/9/1352.full.pdf}, journal = {Cancer Biology \& Medicine} }