Abstract
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 lncRNAs and their relationship to immune microenvironment in breast cancer remain 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 female 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. A ferroptosis-related lncRNAs signature was constructed with univariate and multivariate Cox regression analyses in the training cohort, and its prognostic value was further tested in the validation cohort. Results: An 8-ferroptosis-related-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. Multivariate Cox regression analysis showed the risk score was an independent prognostic indicator. Receiver operating characteristic curve (ROC) analysis proved the predictive accuracy of the signature. 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.
Highlights
Breast cancer is the leading cause of female death worldwide (Bray et al, 2018)
13,683 Long non-coding RNAs (lncRNAs) were identified by analyzing the RNA-seq data of the breast cancer patients, among which 2,877 lncRNAs were
We analyzed the prognostic role of ferroptosis-related lncRNAs in patients receiving anti-HER2 therapy, and the results showed no significant difference in prognosis between patients with high- and low-risk score (Figure 4E)
Summary
Breast cancer is the leading cause of female death worldwide (Bray et al, 2018). With the development in the diagnosis and treatment for breast cancer (Pondé et al, 2019; Ruddy and Ganz, 2019), the survival rate of breast cancer patients has been significantly improved, up to 90% of 5-year survival rate (DeSantis et al, 2019). Another study has reported that GSK3β/Nrf signaling pathway was activated in breast cancer, increasing the expression level of Nrf to resist ferroptosis (Wu et al, 2020). These studies suggest that resistance of ferroptosis is important for the progression of breast cancer. The current studies about relationship between breast cancer and ferroptosis are limited, the association between ferroptosis and prognosis of breast cancer patients remains unclear. Ferroptosis, a regulated cell death which is driven by the iron-dependent peroxidation of lipids, plays an important role in cancer. The prognostic role of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer remain unclear. This study aimed to explore the potential prognostic value of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer
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