Research Paper Volume 15, Issue 15 pp 7760—7780

MYEF2: an immune infiltration-related prognostic factor in IDH-wild-type glioblastoma

Yunxiao Zhang1, *, , Yunyu Wen1, *, , Jing Nie1, *, , Tong Wang2, , Gang Wang1, , Qiaoping Gao3, , Yongfu Cao4, , Hai Wang1, , Songtao Qi1, , Sidi Xie1, ,

  • 1 Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, PR China
  • 2 Department of Neurosurgery, The Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang 621000, Sichuan, PR China
  • 3 Department of Medical Quality Management, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, PR China
  • 4 Neurosurgery, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, Guangdong, PR China
* Equal contribution and share first authorship

Received: March 8, 2023       Accepted: July 15, 2023       Published: August 8, 2023      

https://doi.org/10.18632/aging.204939
How to Cite

Copyright: © 2023 Zhang 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

Glioblastoma (GBM) is the most malignant and prevalent primary brain tumor. In this study, weighted gene coexpression network analysis (WGCNA) was performed to analyze RNA binding protein (RBP) expression data from The Cancer Genome Atlas (TCGA) for the IDH-wild type GBM cohort. The CIBERSORT algorithm quantified the cellular composition of immune cells and was used to identify key modules associated with CD8+ T cell infiltration. Coexpression networks analysis and protein-protein interaction (PPI) network analysis was used to filter out central RBP genes. Eleven RBP genes, including MYEF2, MAPT, NOVA1, MAP2, TUBB2B, CDH10, TTYH1, PTPRZ1, SOX2, NOVA2 and SCG3, were identified as candidate CD8+ T cell infiltration-associated central genes. A Cox proportional hazards regression model and Kaplan-Meier analysis were applied to identify candidate biomarkers. MYEF2 was selected as a prognostic biomarker based on the results of prognostic analysis. Flow Cytometric Analysis indicated that MYEF2 expression was negatively correlated with dysfunctional CD8+ T cell markers. Kaplan–Meier survival analysis (based on IHC staining) revealed that GBM patients with elevated MYEF2 expression have a better prognosis. Knockdown of MYEF2 in GBM cells via in vitro assays was observed to promote cell proliferation and migration. Our study suggests that MYEF2 expression negatively correlates with T cell exhaustion and tumor progression, rendering it a potentially valuable prognostic biomarker for GBM.

Abbreviations

GBM: Glioblastoma; WGCNA: Weighted gene coexpression network analysis; RBP: RNA-binding protein; TCGA: The Cancer Genome Atlas; PPI: Protein–protein interaction; IHC: Immunohistochemistry; TMZ: Temozolomide; TTF: Tumour-treating fields; TAMs: Tumour-associated macrophages; TOM: Topological overlap measure; GS: Gene significance; MS: Module significance; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; GSEA: Gene set enrichment analysis; MYEF2: Myelin expression factor 2 gene; TIICs: Tumour-infiltrating immune cells; MBP: Myelin basic protein; OPC: Oligodendrocyte progenitor cell; ATLL: Adult T cell leukaemia/lymphoma.