• Lijuan Shen, Youwu He, Chunhui Fang, Haiyan Qiu, Qing Chen, Fang Huang, and Zhengyuan Wu.
• Department of Hand Plastic Surgery, The First People's Hospital of Linping District, Hangzhou, China.
• Medicine (Baltimore). 2022 Dec 16; 101 (50): e32301e32301.

AbstractExcess Cu can cause cell death as a cofactor for essential enzymes. The relationship between cuproptosis-associated genes (CAGs) and breast cancer (BR) is not completely investigated. Here, the transcriptome expression and mutation profile data of BR samples from the Cancer Genome Atlas database were retrieved to identify CAGs. Patients with BR were clustered using consensus clustering. A least absolute shrinkage and selection operator analysis was then performed to construct a CAGs risk signature. As a result, all 13 cuproptosis regulators were significantly differentially expressed between BR and normal samples; among them, 9 cuproptosis genes were correlated with prognoses. Patients with BR were separated into 2 clusters that were associated with patient survival, clinical phenotypes, and immune infiltration, Based on the components of cuproptosis. Subsequently, genes differentially expressed between clusters were obtained, and 11 CAGs were ultimately incorporated into the risk signature. Functional analyses revealed that the risk signature correlated with patient outcomes, ER, PR, HER2 expression, and BR IHC subtypes. Additionally, immune microenvironment analyses showed that CAGs-high-risk patients exhibited lower immune cell infiltration and immune functions. Furthermore, high-risk BR patients had higher TMB, lower immune checkpoint expression, higher m6A gene expression, and higher tumor stemness. Finally, the immunophenoscore analysis revealed that the risk signature could potentially predict the immune response in BR and help guide the application of various immunotherapeutic drugs. Overall, the newly constructed CAGs risk signature presented a predictive value for the prognosis and tumor microenvironment of BR patients and can be further used in the guidance of immunotherapy for BR.Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

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