Abstract
Purpose Ephrin B1 (EFNB1), the Eph-associated receptor tyrosine kinase ligand, is suggested to have an important function in neurodevelopment. However, its contribution to glioblastoma multiforme (GBM) remains uncertain. This study aimed to determine the prognostic power and immune implication of EFNB1 in GBM. Methods We first identified differentially coexpressed genes within GBM relative to noncarcinoma samples from GEO and TCGA databases by WGCNA. The STRING online database and the maximum cluster centrality (MCC) algorithm in Cytoscape software were used to design for predicting protein-protein interactions (PPI) and calculating pivot nodes, respectively. The expression of hub genes in cancer and noncancer tissues was verified by an online tool gene expression profile interactive analysis (GEPIA). Thereafter, the TISIDB online tool with Cox correlation regression method was employed to screen for immunomodulators associated with EFNB1 and to model the risk associated with immunomodulators. Results Altogether 201 differentially expressed genes (DEGs) were discovered. After that, 10 hub genes (CALB2, EFNB1, ENO2, EPHB4, NES, OBSCN, RAB9B, RPL23A, STMN2, and THY1) were incorporated to construct the PPI network. As revealed by survival analysis, EFNB1 upregulation predicted poor overall survival (OS) for GBM cases. Furthermore, we developed a prognostic risk signature according to the EFNB1-associated immunomodulators. Kaplan–Meier survival analysis and receiver operating characteristic method were adopted for analysis, which revealed that our signature showed favorable accuracy of prognosis prediction. Finally, EFNB1 inhibition was found to block cell proliferation and migration in GBM cells. Conclusion The above results indicate that EFNB1 participates in cancer immunity and progression, which is the candidate biomarker for GBM.
Highlights
Glioblastoma multiforme (GBM) is a central nervous system (CNS) cancer with high malignancy grade and aggression
By performing Weighted Gene Coexpression Network Analysis (WGCNA), we obtained altogether 7 modules from GSE108474 and 9 from GBM-TCGA
More and more articles suggest that abnormal mRNA shearing is related to cancer migration, cell proliferation, apoptosis, angiogenesis, and metabolism [15–17]
Summary
Glioblastoma multiforme (GBM) is a central nervous system (CNS) cancer with high malignancy grade and aggression. According to the World Health Organization (WHO) classification published in 2016, GBM is classified as a grade IV glioma [1]. With the advancements of medical science, in addition to surgery, chemoradiotherapy, and molecular targeted therapy, novel immunotherapy has been added to the multimode therapy for cancer. Immunotherapy is gradually gaining ground in antitumor therapy. It is well known that the discovery and application of PD-1 and its ligands PD-L1 and CTLA-4 have revolutionized the treatment of tumors [2, 3]. Multiple immunotherapies have been approved by the FDA for a variety of tumors [4]. GBM patients benefit little from immunotherapy [5, 6]. Is may be due to its unique anatomical location, lymphatic drainage of the CNS, blood- GBM patients benefit little from immunotherapy [5, 6]. is may be due to its unique anatomical location, lymphatic drainage of the CNS, blood-
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