Comprehensive Analysis of Ferroptosis-Related LncRNAs in Breast Cancer Patients Reveals Prognostic Value and Relationship With Tumor Immune Microenvironment

Abstract

Background: Breast cancer (BC) is a heterogeneous malignant tumor, leading to the second major cause of female mortality. This study aimed to establish an in-depth relationship between ferroptosis-related LncRNA (FRlncRNA) and the prognosis as well as immune microenvironment of the patients with BC.Methods: We downloaded and integrated the gene expression data and the clinical information of the patients with BC from The Cancer Genome Atlas (TCGA) database. The co-expression network analysis and univariate Cox regression analysis were performed to screen out the FRlncRNAs related to prognosis. A cluster analysis was adopted to explore the difference of immune microenvironment between the clusters. Furthermore, we determined the optimal survival-related FRLncRNAs for final signature by LASSO Cox regression analysis. Afterward, we constructed and validated the prediction models, which were further tested in different subgroups.Results: A total of 31 FRLncRNAs were filtrated as prognostic biomarkers. Two clusters were determined, and C1 showed better prognosis and higher infiltration level of immune cells, such as B cells naive, plasma cells, T cells CD8, and T cells CD4 memory activated. However, there were no significantly different clinical characters between the clusters. Gene Set Enrichment Analysis (GSEA) revealed that some metabolism-related pathways and immune-associated pathways were exposed. In addition, 12 FRLncRNAs were determined by LASSO analysis and used to construct a prognostic signature. In both the training and testing sets, patients in the high-risk group had a worse survival than the low-risk patients. The area under the curves (AUCs) of receiver operator characteristic (ROC) curves were about 0.700, showing positive prognostic capacity. More notably, through the comprehensive analysis of heatmap, we regarded LINC01871, LINC02384, LIPE-AS1, and HSD11B1-AS1 as protective LncRNAs, while LINC00393, AC121247.2, AC010655.2, LINC01419, PTPRD-AS1, AC099329.2, OTUD6B-AS1, and LINC02266 were classified as risk LncRNAs. At the same time, the patients in the low-risk groups were more likely to be assigned to C1 and had a higher immune score, which were consistent with a better prognosis.Conclusion: Our research indicated that the ferroptosis-related prognostic signature could be used as novel biomarkers for predicting the prognosis of BC. The differences in the immune microenvironment exhibited by BC patients with different risks and clusters suggested that there may be a complementary synergistic effect between ferroptosis and immunotherapy.

A novel Cuproptosis-related LncRNA signature to predict prognosis in hepatocellular carcinoma

“…Among the six lncRNA involved in our signature, AC099329.2 and DNMBP-AS1 were protective lncRNA in HCC patients, while AC138904.1, DEPDC1-AS1, GIHCG, and AC145343.1 were risk lncNRAs. AC099329.2 and DNMBP-AS1 have been reported to be strongly associated with ferroptosis and could be used as a novel biomarker for predicting Breast Cancer prognosis 39 , 40 , and DEPDC1-AS1 has also been shown to be significantly correlated with ferroptosis and may serve as a good prognostic marker for lung adenocarcinoma 41 , 42 . However, their functions and mechanisms of them have not been reported so far in HCC.…”

Identification and validation of a novel ferroptosis-related 11-lncRNA prognostic signature related to immune infiltration and drug sensitivity in ccRCC

“…Further research found that 3 risk lncRNAs (LINC01871, PRKAR1B-AS1 and CYTOR) were the key ferroptosisrelated lncRNAs in the regulation of tumor immune in ltration. Xu et al and Mao et al have demonstrated that LINC01871 and CYTOR were associated with the immune in ltration of breast cancer (BC) and bladder urothelial carcinoma (BLCA), respectively [27,31]. This nding could provide important guidance for future ccRCC therapeutic strategy targeting ferroptosis.…”

“…Tian et al found that CYTOR promoted cell proliferation and tumor growth via miR-125b/SEMA4C axis in hepatocellular carcinoma [26]. Xu et al found that LINC01871 was a ferroptosis-related lncRNA, which could be used as novel biomarkers for predicting the prognosis of breast cancer (BC) [27]. However, there are currently no research reports on the other 4 lncRNAs (AL353801.1, LHFPL3-AS2, PRKAR1B-AS1 and AC107021.2).…”

Construction of five cuproptosis-related lncRNA signature for predicting prognosis and immune activity in skin cutaneous melanoma

“…This is consistent with our study, indicating that MALINC1 plays an important role in the progression of SKCM. It is worth noting that lncRNA HSD11B1-AS1 also proved to play a crucial role in the progress of SKCM ( Liu et al, 2022 ) and breast cancer ( Xu et al, 2021 ). Liu et al confirmed that lncRNA HSD11B1-AS1served as a protective factor inhibits the proliferation, migration, and invasion of SKCM by multiple functional experiments ( Liu et al, 2022 ).…”