An Immune-Related Long Noncoding RNA Pair as a New Biomarker to Predict the Prognosis of Patients in Breast Cancer.

Abstract

Background: Immune-related long non-coding RNAs (irlncRNAs) might remodel the tumor immune microenvironment by changing the inherent properties of tumor cells and the expression of immune genes, which have been used to predict the efficacy of immunotherapy and the prognosis of various tumors. However, the value of irlncRNAs in breast cancer (BRCA) remains unclear. Materials and Methods: Initially, transcriptome data and immune-related gene sets were downloaded from The Cancer Genome Atlas (TCGA) database. The irlncRNAs were extracted from the Immunology Database and Analysis Portal (ImmPort) database. Differently expressed irlncRNAs (DEirlncRNAs) were further identified by utilizing the limma R package. Then, univariate and multivariate Cox regression analyses were conducted to select the DEirlncRNAs associated with the prognosis of BRCA patients. In addition, the univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were performed to determine the DEirlncRNA pairs with the independent prediction capability of prognosis in BRCA patients. Finally, the chosen DEirlncRNA pair would be evaluated in terms of survival time, clinicopathological characteristics, tumor-infiltrating immune cells, immune checkpoints (ICs), signaling pathways, and potential small-molecule drugs. Results: A total of 21 DEirlncRNA pairs were extracted, and among them, lncRNA MIR4435-2HG and lncRNA U62317.1 were chosen to establish a risk signature that served as an independent prognostic biomarker in BRCA patients. Patients in the high-risk group had a worse prognosis than those in the low-risk group, and they also had an abundance of infiltration of CD4+ T and CD8+ T cells to enhance the immune response to tumor cells. Furthermore, the risk signature showed a strong correlation with ICs, signaling pathways, and potential small-molecule drugs. Conclusion: Our research revealed that the risk signature independent of specific DEirlncRNA pair expression was closely associated with the prognosis and tumor immune microenvironment in BRCA patients and had the potential to function as an independent prognostic biomarker and a predictor of immunotherapy for BRCA patients, which would provide new insights for BRCA accurate treatment.