A Novel Oxidative Stress-Related lncRNA Signature That Predicts the Prognosis and Tumor Immune Microenvironment of Breast Cancer.

Abstract

Background The association between oxidative stress and lncRNAs within the cancer-related researching field has been a controversial subject. At present, the exact function of oxidative stress as well as lncRNAs exert in breast cancer (BC) are still unclear. Therefore, the present study examined the lncRNAs oxidative stress-related in BC. Methods Transcriptome data of BC obtained from TCGA (The Cancer Genome Atlas) database were used to generate synthetic matrices. Patients with breast cancer were randomly assigned to training, testing, or combined groups. The prognostic signature of oxidative stress was created using the selection operator Cox regression method, and the difference in prognosis between groups was examined using Kaplan-Meier curves, the accuracy of which was calculated using a receiver-operating characteristic-area through the curve (ROC-AUC) analysis with internal validation. Also, the Gene Set Enrichment Analyses (GSEA) was applied for the analysis of the risk groups. To conclude, the half-maximal inhibitory concentration (IC50) of these groups were investigated by immunoassay assay. Results A model based on 7 lncRNAs related to oxidative stress was proposed, and the calibration plots and projected prognosis matched well. For prognosis at 5, 3, and 1 year, the area under the ROC curve (AUC) values were 0.777, 0.777, and 0.759. The functions of target genes identified by GSEA appear to be mainly expressed in metabolism, signal transduction, tumorigenesis, and also the progression. The remarkable differences in IC50 and gene expression between risk groups in this study provide a deep insight for further systemic treatment. Higher macrophage scores were acquired in the high-risk group, of which patients showed more response to conventional chemotherapy drugs, such as AKT inhibitor VIII and Lapatinib, as well as immunotherapy strategies including anti-CD80, TNF SF4, CD276, and NRP1. Conclusion The prognosis of breast cancer can be independently predicted by the markers, which sheds light on further research of the specific role of lncRNAs which are oxidative stress-related and clinical treatment of breast cancer.