Bioinformatics prediction and experimental verification identify B4GALT1 as a diagnostic biomarker of glioblastoma.

in International journal of biological macromolecules by Xiangdong Lu, Bingcheng Wang, Peng Qiu, Tao Xin

TLDR

  • This study identified a glycolysis-related gene signature associated with poor prognosis in glioblastoma, including B4GALT1, and found that B4GALT1 may serve as a promising prognostic biomarker for GBM therapy.

Abstract

Glycolysis plays a key role in the progression of glioblastoma (GBM). Gene expression and clinical information were obtained from The Cancer Genome Atlas, Genotype-Tissue Expression, the Chinese Glioma Genome Atlas database, and five Gene Expression Omnibus datasets. Twenty-one prognosis-related glycolytic differentially expressed genes were identified. The glycolysis-related gene signature associated with poor prognosis was constructed using six upregulated glycolytic genes, including beta-1, 4-galactosyltransferase1 (B4GALT1), and beta-glucuronidase (GUSB). The main immune cell types in GBM samples were M2 macrophages and resting memory CD4+ T cells, and a high-risk score was associated with high neutrophil infiltration. Clinical GBM tissues exhibited higher B4GALT1 and GUSB expression than normal tissues. B4GALT1 expression positively correlated with multiple immune checkpoint genes, and the knockdown of B4GALT1 inhibited the proliferation of GBM cells in vitro and in vivo. Knockdown of B4GALT1 reduced lactic acid levels and increased those of tumor necrosis factor-α and interferon-γ. Accordingly, a prognostic model based on six glycolytic genes could be used to predict poor prognosis and high immune infiltration in patients with GBM. Thus, B4GALT1 may serve as a promising prognostic biomarker for GBM therapy.

Overview

  • This study identified 21 prognosis-related glycolytic differentially expressed genes in glioblastoma (GBM) and constructed a glycolysis-related gene signature associated with poor prognosis.
  • The study found that high-risk scores were associated with high neutrophil infiltration and identified six upregulated glycolytic genes, including beta-1, 4-galactosyltransferase1 (B4GALT1) and beta-glucuronidase (GUSB).
  • The primary objective of the study was to investigate the role of glycolysis in GBM and to identify potential biomarkers for predicting poor prognosis and high immune infiltration in patients with GBM.

Comparative Analysis & Findings

  • Comparison of gene expression and clinical information from various databases identified 21 prognosis-related glycolytic differentially expressed genes in GBM.
  • The study found that high-risk scores were associated with high neutrophil infiltration, and that B4GALT1 expression positively correlated with multiple immune checkpoint genes.
  • Knockdown of B4GALT1 inhibited the proliferation of GBM cells in vitro and in vivo, and reduced lactic acid levels while increasing those of tumor necrosis factor-α and interferon-γ.

Implications and Future Directions

  • The study's findings suggest that B4GALT1 may serve as a promising prognostic biomarker for GBM therapy.
  • Future studies could investigate the mechanisms by which B4GALT1 influences GBM progression and explore the potential of B4GALT1-targeting therapies.
  • Developing a prognostic model based on the six glycolytic genes could help guide treatment decisions and improve patient outcomes for GBM patients.