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

乳腺癌 医学 接收机工作特性 癌变 氧化应激 转录组 比例危险模型 肿瘤科 曲线下面积 癌症 生存分析 内科学 基因 计算生物学 生物信息学 癌症研究 基因表达 生物 遗传学
作者
Jinlai Zhao,Haiyan Ma,Ruigang Feng,Dan Li,Bowen Liu,None YueYu,Xuchen Cao,Xin Wang
出处
期刊:Journal of Oncology [Hindawi Publishing Corporation]
卷期号:2022: 1-22
标识
DOI:10.1155/2022/9766954
摘要

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.
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