A New Necroptosis-Related lncRNA Signature Predicts the Prognosis and Tumor Immune Microenvironment of Breast Cancer Patients

Abstract Background: The issue of relationship between necroptosis and lncRNAs has been a controversial subject within cancer-related research. Currently, the exact role of necroptosis and lncRNAs exerted in breast cancer (BC) remains to be discovered. Therefore, the necroptosis-related lncRNAs in BC are explored in this study.Methods: BC transcriptome data were obtained from the TCGA (The Cancer Genome Atlas) database to create synthetic matrices. Analysis approaches of univariate Cox regression and co-expression were combined to identify necroptosis-related prognostic lncRNAs. Then multivariate Cox regression and Lasso approaches were performed to acquire necroptosis-related lncRNAs, from which the predictive necroptosis-related lncRNA signature was constructed. Next, calibration curves, the time-dependent receiver operating characteristics (ROCs), ,and a nomogram were obtained, and the Kaplan-Meier analysis was performed to verify and evaluate the proposed model. Besides, the risk groups were analyzed with the Gene Set Enrichment Analyses (GSEA). Finally, these groups were studied by immune analysis to obtain the predicted half-maximal inhibitory concentration (IC50).Results: A model was proposed based on 10 necroptosis-related lncRNAs, and the calibration plots accorded well with the predicted prognosis. For the 1-, 3-, and 5-year prognosis, the area under the ROC curve (AUC) values were 0.71, 0.729 and 0.707 respectively. GSEA identified that the functions of target genes located primarily in immunity, metabolism, as well as tumor occurrence and development. The remarkable differences in IC50 and gene expression between risk groups gave a significant insight for further systemic treatments. Besides, higher macrophage scores were found in the high-risk group, in which the patients were more sensitive to conventional chemotherapy drugs (such as AKT inhibitor VIII and saracatinib) and anti-CD80, TNF SF4, and CD276 immunotherapies.Conclusion: The prognosis of BC patients can be independently predicted by the predictive signatures, which shines new insights on further exploration of how necroptosis-related lncRNAs exactly works in BC and clinical treatments of BC.