Abstract

Objective We investigated the expression patterns, potential functions, unique prognostic value, and potential therapeutic targets of E2Fs in brain and CNS cancer and tumor-infiltrating immune cell microenvironments. Methods We analyzed E2F mRNA expression levels in diverse cancer types via Oncomine and GEPIA databases, respectively. Moreover, we evaluated the prognostic values using GEPIA database and TCGAportal database and the correlation of E2F expression with immune infiltration and the correlation between immune cell infiltration and GBM and LGG prognosis via TIMER database. Then, cBioPortal, GeneMANIA, and DAVID databases were used for mutation analysis, PPI network analysis of coexpressed gene, and functional enrichment analysis. Results E2F1-8 expression increased in most cancers, including brain and CNS cancer. Higher expression in E2F1, 2, 4, 6, 7, and 8 indicated poor OS of LGG. Higher E2F3–6 and E2F1–8 expressions correlated with poor prognosis and increased immune infiltration levels in CD8+ T cells, macrophages, neutrophils, and DCs in GBM and CD8+ T cells, B cells, CD4+ T cells, neutrophils, macrophages, and DCs in LGG, respectively. Conclusion E2F1–8 and E2F2–8 could be hopeful prognostic biomarkers of GBM and LGG, respectively. E2F3–6 and E2F1–8 could be likely therapeutic targets in patients with immune cell infiltration of GBM and LGG, respectively.

Highlights

  • E2F transcription factors CNS (E2Fs), as a set of genes encoding transcription factor family (TFs) in higher eukaryotes, play an essential role in cell cycle regulation and DNA synthesis [1]

  • We systematically analyzed the expressions of E2Fs in brain and CNS cancer tissues, assessed their prognostic value, and investigated their correlation with tumorinfiltrating immune cells

  • Bioinformatics analysis indicated that the increased expressions of E2F1, 2, and 5–8 in Glioblastoma multiforme LGG (GBM) tissues and those of E2F5 and 6 in LGG tissues may play a vital role in oncogenesis

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Summary

Introduction

E2Fs, as a set of genes encoding transcription factor family (TFs) in higher eukaryotes, play an essential role in cell cycle regulation and DNA synthesis [1]. A report demonstrating that increased expression in E2F3a played a significant role in the development of glioma. Almost 80% of malignant brain cancers are gliomas [4]. Current immunotherapies, for example, anti-CTLA4, demonstrated poor clinical efficacy in brain tumors [9]. After the diagnosis of malignant brain and CNS tumors, the overall 5-year relative survival rate was 32.1%, of which the survival rate was only 4.9% after the diagnosis of GBM (glioblastoma multiforme) [4], and metastasis often leads to a poor prognosis. There is an urgent need to identify new therapeutic targets in the brain and CNS cancer so as to effectively improve the accuracy of treatment

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