Affiliation:
1. the First Hospital of China Medical University
Abstract
Abstract
Background
Breast cancer is the most prevalent malignancy worldwide and the leading culprit for women death. Cuproptosis is a novel and promising modality of tumor cell death whose relationship with lncRNAs remains shrouded in veil. Studies in cuproptosis-related lncRNAs can aid on the clinical management of breast cancer and provide 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 they got. Cox regression and 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 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 mutation burden and suppressed anti-tumor immunity. Besides, cuproptosis-related lncRNAs were associated with expression of immune checkpoint inhibitors, 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 immune microenvironment, TMB, m6a and drug sensitivity in breast cancer, which may provide basis for future anti-tumor drug development.
Publisher
Research Square Platform LLC