The cuproptosis-related signature predicts prognosis and indicates immune microenvironment in breast cancer

Abstract

Breast cancer (BC) is the most diagnosed cancer in women. Cuproptosis is new regulated cell death, distinct from known death mechanisms and dependent on copper and mitochondrial respiration. However, the comprehensive relationship between cuproptosis and BC is still blank until now. In the present study, we acquired 13 cuproptosis-related regulators (CRRs) from the previous research and downloaded the RNA sequencing data of TCGA-BRCA from the UCSC XENA database. The 13 CRRs were all differently expressed between BC and normal samples. Using consensus clustering based on the five prognostic CRRs, BC patients were classified into two cuproptosis-clusters (C1 and C2). C2 had a significant survival advantage and higher immune infiltration levels than C1. According to the Cox and LASSO regression analyses, a novel cuproptosis-related prognostic signature was developed to predict the prognosis of BC effectively. The high- and low-risk groups were divided based on the risk scores. Kaplan-Meier survival analysis indicated that the high-risk group had shorter overall survival (OS) than the low-risk group in the training, test and entire cohorts. GSEA indicated that the immune-related pathways were significantly enriched in the low-risk group. According to the CIBERSORT and ESTIMATE analyses, patients in the high-risk group had higher infiltrating levels of antitumor lymphocyte cell subpopulations and higher immune score than the low-risk group. The typical immune checkpoints were all elevated in the high-risk group. Furthermore, the high-risk group showed a better immunotherapy response than the low-risk group based on the Tumor Immune Dysfunction and Exclusion (TIDE) and Immunophenoscore (IPS). In conclusion, we identified two cuproptosis-clusters with different prognoses using consensus clustering in BC. We also developed a cuproptosis-related prognostic signature and nomogram, which could indicate the outcome, the tumor immune microenvironment, as well as the response to immunotherapy.

Prognostic Significance of Cuproptosis-Related Gene Signatures in Breast Cancer Based on Transcriptomic Data Analysis

“…The area under the ROC curve in both the training and validation sets at 1, 3 and 5 years was (AUC) 0.686, 0.722 and 0.727, and 0.626, 0.663 and 0.678, respectively ( Figure 4 F and Figure 5 C). In addition, we compared our risk model with other established models and found that the AUC of our risk model was higher than that of others ( Figure S3A–F ) [ 17 , 18 ].…”

“…Our study also showed some limitations. Firstly, Jia li et al [ 18 ] recently reported a model based on 13 differentially expressed cuproptosis regulators (between breast cancer and normal samples) selected from the original report firstly discovering cuproptosis [ 5 ], which could efficiently predict prognosis and even response to immunotherapy. Our study applied expanded cuproptosis-related DEGs according to different studies [ 5 , 13 , 14 , 15 , 16 ].…”

Development and validation of cuproptosis-related lncRNA signatures for prognosis prediction in colorectal cancer

“…Wang et al [ 32 ] found the involvement of cuproptosis-related genes regulation in Hepatocellular carcinoma (HCC). Li et al [ 33 ] develop the cuproptosis-related prognostic signature to predict the prognosis of breast cancer (BC) through the Cox and Lasso regression analyses. However, studies of the function of CRLs in colorectal cancer (CRC) remain limited.…”

Copper-related genes predict prognosis and characteristics of breast cancer

“…Previous studies mainly focused on the relationship between cuproptosis-related genes and breast cancer ( 67 , 68 ). Our study included not only cuproptosis-related genes but also copper metabolism-related genes to perform a comprehensive analysis of the role of copper-related genes in breast cancer development.…”