Basic Transcription Factor 3 Like 4 Enhances Malignant Phenotypes through Modulating Tumor Cell Function and Immune Microenvironment in Glioma

Am J Pathol. 2024 May;194(5):772-784. doi: 10.1016/j.ajpath.2024.01.011. Epub 2024 Feb 5.

Abstract

Recent investigations into the tumor microenvironment have provided insights into the limited response of glioma progression to immunotherapy. However, the specific involvement of basic transcription factor 3 like 4 (BTF3L4) in glioma progression and its correlation with immune cell infiltration remain areas of uncertainty that require further exploration. In the current study, BTF3L4 expression was delineated by using gene expression profiling/interactive analysis and multiplex-immunohistologic staining of tissue microarrays. The prognostic value of BTF3L4 was then assessed by using Cox regression models and Kaplan-Meier methods, and in vitro experiments were conducted to investigate how BTF3L4 protein affects the proliferation, migration, and invasion capabilities of glioma cells. Furthermore, the CIBERSORT and ESTIMATE methods were used to quantify immune cells that correlate to BTF3L4 expression, and multiplex-immunohistologic staining was applied to investigate its correlation with infiltrated immune cells in glioma tissues. These findings revealed higher BTF3L4 expression in glioma tissues compared with non-tumor brain tissues, which correlated with clinical characteristics and worse patient prognosis. Furthermore, the down-regulation of BTF3L4 protein in the glioma cell line had a detrimental effect on cell migration, invasion, and proliferation. In addition, the association between BTF3L4 and key immune molecules in glioma, particularly with the infiltration of CD66B+ neutrophils and programmed death ligand 1 expression, was identified. These results highlight the prognostic significance of BTF3L4 and propose BTF3L4 as a potential target for glioma immune therapy.

MeSH terms

  • Cell Line
  • Cell Movement
  • Down-Regulation
  • Glioma* / genetics
  • Humans
  • Prognosis
  • Transcription Factor 3*
  • Tumor Microenvironment

Substances

  • Transcription Factor 3