A signature of cuproptosis-related lncRNAs predicts prognosis and provides basis for future anti-tumor drug development in breast cancer.

BACKGROUND: Breast cancer is the most prevalent malignancy worldwide and the leading culprit for women's death. Cuproptosis is a novel and promising modality of tumor cell death and the relationship with long non-coding RNAs (lncRNAs) remains shrouded in a veil. Studies in cuproptosis-related lncRNAs can aid in the clinical management of breast cancer and provide a basis for anti-tumor drug development.

METHODS: RNA-Seq data, somatic mutation data, and clinical information were downloaded from The Cancer Genome Atlas (TCGA). Patients were divided into high- and low-risk groups according to the risk score. Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were used to select prognostic lncRNAs to construct a risk score system. Its' prognostic value was confirmed in the training and validation cohorts subsequently. Functional analysis regarding cuproptosis-related lncRNAs was performed.

RESULTS: Eighteen cuproptosis-related lncRNAs were identified and 11 of them including AL023882.1 , AC091588.1 , AC138028.2 , AC027514.1 , AL592301.1 , LRRC8C-DT , MFF-DT , NIFK-AS1 , MECOM-AS1 , OTUD6B-AS1 and RNF32-AS1 were selected for risk score system construction. The risk score was confirmed as an independent prognostic factor and patients in the high-risk group had a worse prognosis. A nomogram based on the independent prognostic factors was constructed for clinical decision aids. Further analyses revealed that patients in the high-risk group faced a heavier tumor mutational burden (TMB) and suppressed anti-tumor immunity. Besides, cuproptosis-related lncRNAs were associated with the expression of immune checkpoint inhibitors, N6-adenylate methylation (m6a), and drug sensitivity in breast cancer.

CONCLUSIONS: A prognostic risk score system with satisfactory predictive accuracy was constructed. Besides, cuproptosis-related lncRNAs can influence the immune microenvironment, TMB, m6a, and drug sensitivity in breast cancer, which may provide a basis for future anti-tumor drug development.