A Ferroptosis-Related lncRNAs Signature Predicts Prognosis and Immune Microenvironment for Breast Cancer

摘要

Background: Ferroptosis, a regulated cell death which is driven by the iron-dependent peroxidation of lipids, plays an important role in cancer. However, studies about ferroptosis-related Long non-coding RNAs (lncRNAs) in breast cancer (BC) are limited. Besides, the prognostic role of ferroptosis-related lncRNA and its relationship to immune microenvironment in breast cancer remains unclear. This study aimed to explore the potential prognostic value of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer. Methods: RNA-sequencing data of breast cancer patients were downloaded from TCGA database. 937 patients were randomly separated into training or validation cohort in 2:1 ratio. Ferroptosis-related lncRNAs were screened by Pearson correlation analysis with 239 reported ferroptosis-related genes and were overlapped with differentially expressed lncRNAs between tumor tissues and normal tissues. A ferroptosis-related lncRNAs signature was constructed with univariate and multivariate Cox regression analyses in the training cohort, and its prediction value for survival was further tested in the validation cohort. Results: An 8-lncRNAs signature was developed by multivariate Cox regression analysis to divide patients into two risk groups. Patients in the high-risk group had worse prognosis than patients in the low-risk group (P 0.001 in the training cohort, P=0.0049 in the validation cohort). Multivariate Cox regression analysis showed the risk score was an independent predictor for overall survival (OS). Receiver operating characteristic curve (ROC) analysis proved the signature's predictive accuracy. The area under time-dependent ROC curve (AUC) reached 0.853 at 1 year, 0.802 at 2 years, 0.740 at 5 years in the training cohort and 0.791 at 1 year, 0.778 at 2 years, 0.722 at 5 years in the validation cohort. Further analysis demonstrated that immune-related pathways were significantly enriched in the high-risk group. Analysis of the immune cell infiltration landscape showed that breast cancer in the high-risk group tended be immunologically “cold”. Conclusion: We identified a novel ferroptosis-related lncRNA signature which could precisely predict the prognosis of breast cancer patients. Ferroptosis-related lncRNAs may have a potential role in the process of anti-tumor immunity and serve as therapeutic targets for breast cancer.