Affiliation:
1. Chengdu First People's Hospital
Abstract
Abstract
Background: Several studies had shown that the ubiquitin D (UBD) could be a potential prognostic factor in various cancers. However, the prognostic value of UBD in glioma remained unknown.
Materials and Methods: The differences of UBD expression in glioma were analyzed based on the datasets of the Cancer Genome Atlas database (TCGA) and Chinese Glioma Genome Atlas (CGGA) and identified by qRT-PCR and western blot. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene set enrichment analysis (GSEA) were used to determine the functions of UBD. Moreover, the protein network of UBD was constructed using Cytoscape software. A spearman’s correlation analysis was performed to determine the association between UBD expression and immune cell infiltration. Additionally, a logistic regression analysis was performed to analyze the association between UBD expression and the clinicopathological characteristics of the glioma patients. The diagnostic and prognostic predictive values of UBD were evaluated using the Kaplan–Meier survival curves, Cox regression analysis, diagnostic receiver operating characteristic (ROC) curves, and nomogram model. Finally, the biological function of UBD was determined by wound healing assays, transwell assays, EdU and colony formation assays.
Results: UBD expression in glioma samples was considerably increased, which was associated with the P53 pathway, angiogenesis, inflammatory response, TNFα -NF-κB signaling, IL-6-JAK-STAT3 signaling, PI3K-AKT-mTOR signaling, TGF-β signaling, KRAS signaling, as well as hypoxia, and epithelial-mesenchymal transition (EMT). UBD expression correlated with the infiltration level of immune cells through the ssGSEA method. High UBD expression was an independent prognostic factor of glioma in TCGA. ROC curve analysis showed good diagnostic efficacy of UBD in glioma. Furthermore, UBD could increase the migration, invasion and proliferation ability of glioma cells.
Conclusion: UBD may be a potential prognostic marker and therapeutic target in glioma.
Publisher
Research Square Platform LLC
Reference34 articles.
1. 1. Fan H, Xie X, Kuang X, Du J, Peng F. MicroRNAs, Key Regulators in Glioma Progression as Potential Therapeutic Targets for Chinese Medicine. Am J Chin Med. 2022:1–27.
2. 2. Xu S, Tang L, Li X, Fan F, Liu Z. Immunotherapy for glioma: Current management and future application. Cancer Lett. 2020;476:1–12.
3. 3. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131(6):803 − 20.
4. 4. Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY, Olson JJ. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin. 2010;60(3):166 − 93.
5. 5. Cloughesy TF, Mochizuki AY, Orpilla JR, Hugo W, Lee AH, Davidson TB, et al. Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat Med. 2019;25(3):477 − 86.