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.

Integrated bioinformatics analysis of noncoding RNAs with tumor immune microenvironment in gastric cancer

“…LncRNAs have been implicated in facilitating the evasion of immune surveillance by tumor cells through multiple mechanisms, including the promotion of an immunosuppressive microenvironment 26 – 28 . Multiple studies used comprehensive analysis to determine the functions of various lncRNAs in tumor immune microenvironment (TIME) in various cancers, such as colon cancer 29 , clear cell renal cell carcinoma 30 , breast cancer 31 , 32 , lung cancer 33 , 34 , thyroid cancer 35 , adrenocortical adenocarcinoma 36 , bladder cancer 37 , and head and neck squamous cell carcinoma 38 . LncRNA NKILA has demonstrated the ability to initiate apoptosis in tumor-specific T cells, thereby impeding their capacity to infiltrate the tumor, leading to tumor immune evasion 39 .…”

Revealing heterogeneity and damage response in the adult human utricle

“…Among the downregulated genes, we found ELF3, a TF regulator of mesenchymal to epithelial transition 50 ), ID4, a transcriptional target of Notch signalling, and NFIB, which is involved in retinal neuron regeneration processes in zebra sh, chicks, and mice 51 . We also found FZD7, a gene related to the activation of Wnt/β-catenin signalling, and MIR4435-2HG, an immune-related lncRNA, being upregulated 52 . CDH11 was also upregulated; cadherin-11 binds to PDGFRβ and enhances cell proliferation and tissue regeneration via the PDGFR-AKT signalling axis 53 .…”

Senescence-Related lncRNA Signature Predicts Prognosis, Response to Immunotherapy and Chemotherapy in Skin Cutaneous Melanoma

“…Several clinically immune-related lncRNAs including AC009495.2 were identified, and a prognostic model was developed, providing a molecular assessment of immune function and a potential prognosis for patients [ 30 ]. Jiang et al developed a risk signature of lncRNA pairs containing lncRNA U62317.1 and MIR4435-2HG for predicting prognosis of breast cancer patients [ 31 ].…”