Research Paper Volume 15, Issue 15 pp 7616—7636
An angiogenesis-related lncRNA signature predicts the immune microenvironment and prognosis of breast cancer
- 1 Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, People’s Republic of China
- 2 Department of Pathology, Qilu Hospital of Shandong University, Jinan, People’s Republic of China
- 3 Hematology and Oncology Unit, Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, People’s Republic of China
- 4 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, People’s Republic of China
- 5 Department of General Surgery, Affiliated Haian Hospital of Nantong University, Nantong, People’s Republic of China
Received: March 1, 2023 Accepted: July 17, 2023 Published: August 3, 2023
https://doi.org/10.18632/aging.204930How to Cite
Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Both angiogenesis and lncRNAs play crucial roles in the development and progression of breast cancer. Considering the unknown association of angiogenesis and lncRNAs in breast cancer, we aim to identify angiogenesis-related lncRNAs (ARLs) and explore their prognostic value. Here, based on analysis of The Cancer Genome Atlas database, the correlation between ARL and the prognosis and immune infiltration landscape of breast cancer were investigated. Eight ARLs (MAFG−DT, AC097478.1, AL357054.4, AL118556.1, SNHG10, MED14OS, OTUD6B−AS1, and CYTOR) were selected to construct the risk model as a prognostic signature. The survival rate of the patients in the high-risk group was lower than that in the low-risk group. The ARL signature was an independent prognostic predictor, and areas under the curve of 1-, 3-, and 5-year survival were 0.745, 0.695, and 0.699, respectively. The prognostic ARLs were associated with the immune infiltration landscape and could indicate the immune status, immune response, tumor mutational burden, and drug sensitivity of patients with breast cancer. Furthermore, qRT-PCR of clinical samples revealed that OTUD6B−AS1 was correlated with prognostic pathological parameters. OTUD6B−AS1 promoted breast cancer cell proliferation, wound healing, migration, invasion, and human umbilical vein endothelial cells tube formation. Mechanistically, OTUD6B−AS1 regulated EMT- and angiogenesis-related molecules. Taken together, we constructed and verified a robust signature of eight ARLs for the prediction of survival in patients with breast cancer, and the characterization of the immune infiltration landscape. Our findings suggest that OTUD6B−AS1 could be a therapeutic target for patients with breast cancer.
Abbreviations
ARL: Angiogenesis-related lncRNA; TCGA: The Cancer Genome Atlas; ROC: Receiving operating characteristic; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; LASSO: Least absolute shrinkage and selection operator; TMB: Tumor Mutation Burden; PCA: Principal coordinate analysis; OS: Overall survival; AUC: Areas under the curve; RT-qPCR: Real-time quantitative polymerase chain reaction; IPS: Immunophenoscore; GDSC: Genomics of Drug Sensitivity in Cancer; C-index: Calibration diagram and consistency index; ssGSEA: Single sample gene set enrichment analysis; TIDE: Tumor Immune Dysfunction and Exclusion; DEGs: Differential expression genes; ANOVA: Analysis of variance; ICI: Immune cell infiltration landscape; MDSC: Myeloid-derived suppressor cells; Tregs: Regulatory T cells; PPARs: Peroxisome proliferator-activated receptors.