Molecular and clinical features of a potential immunotherapy target ELK3 in glioma

Medicine (Baltimore). 2022 Jul 29;101(30):e29544. doi: 10.1097/MD.0000000000029544.

Abstract

Glioma represents the most prevalent malignant primary brain cancer, and its treatment remains a tremendous challenge. Novel and efficient molecular targets are therefore required for improving diagnosis, survival prediction, and treatment outcomes. Additionally, some studies have shown that immunity is highly associated with glioma progression. Our study aimed to investigate the clinicopathological features, prognostic significance, and immunotherapeutic targetability of ELK3, a member of the erythroblast transformation-specific transcription factor family, in glioma using bioinformatics analyses. ELK3 transcript levels in glioma tissues were evaluated using the Gene Expression Omnibus and The Cancer Genome Atlas databases. Clinical and transcriptomic data of The Cancer Genome Atlas glioma patients were analyzed to identify the molecular and clinical characterizations of ELK3. The prognostic significance of ELK3 was assessed using Cox regression and Kaplan-Meier analysis. The biological pathways related to ELK3 expression were identified by gene set enrichment analysis. The relationships between ELK3 and inflammatory responses, immune cell infiltration, and immune checkpoints were explored using canonical correlation analysis and gene set variation analysis. ELK3 was upregulated in gliomas, and its high expression was correlated with advanced clinicopathologic features and unfavorable prognosis. Gene set enrichment analysis revealed that several immune-related pathways were tightly linked to high ELK3 expression. gene set variation analysis and correlograms demonstrated that ELK3 was robustly associated with inflammatory and immune responses. Correlation analyses indicated that ELK3 was positively associated with infiltrating immune cells and synergistic with several immune checkpoints. ELK3 may serve as a novel marker of poor prognosis and a potential immunotherapeutic target in glioma.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms* / diagnosis
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / therapy
  • Glioma* / genetics
  • Glioma* / metabolism
  • Glioma* / therapy
  • Humans
  • Immunotherapy
  • Prognosis
  • Proto-Oncogene Proteins c-ets

Substances

  • Biomarkers, Tumor
  • Elk3 protein, human
  • Proto-Oncogene Proteins c-ets