Enrichment of branched chain amino acid transaminase 1 correlates with multiple biological processes and contributes to poor survival of IDH1 wild-type gliomas

Aging (Albany NY). 2021 Jan 20;13(3):3645-3660. doi: 10.18632/aging.202328. Epub 2021 Jan 20.

Abstract

Previous studies have reported the association between branched-chain amino acid trasaminase1 (BCAT1) and IDH1 wild-type gliomas. Nonetheless, as a promising target for treatment of primary glioblastoma, comprehensive reports on BCAT1 in gliomas are still lacking. In the present study, we accessed glioma patient cohorts and tissue microarray to evaluate the expression pattern of BCAT1 for determining its prognostic value and its relationship with IDH1 mutation status. Furthermore, we explored the potential regulatory mechanism of BCAT1 in gliomas by comparing the BCAT1 mRNA expression pattern with selected tumor biological signatures. The results showed that BCAT1 is highly expressed in GBM versus lower grade gliomas and could represent the poor survival of IDH1 wild-type gliomas. Moreover, BCAT1 is an independent prognostic factor for glioma patients, high BCAT1 expression is related to unfavorable clinical parameters including older age, IDH wildtype, no 1p/19q codeletion, ATRX wildtype and MGMT unmethylated. Additionally, BCAT1 correlated with apoptosis, hypoxia and angiogenesis processes in gliomas and high expression of BCAT1 revealed higher glycolysis level and increased immunosuppressive status in tumor progression. We concluded that BCAT1 is a strong prognostic factor for glioma patients and involved in the malignant progression of IDH1 wild-type gliomas.

Keywords: IDH1; branched chain amino acid transaminase 1; glioma; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Astrocytoma / genetics*
  • Astrocytoma / metabolism
  • Astrocytoma / pathology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • DNA Methylation
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • Female
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology
  • Glycolysis / genetics
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neovascularization, Pathologic / genetics
  • Oligodendroglioma / genetics*
  • Oligodendroglioma / metabolism
  • Oligodendroglioma / pathology
  • Prognosis
  • Survival Rate
  • Transaminases / genetics*
  • Transaminases / metabolism
  • Tumor Escape / genetics
  • Tumor Hypoxia / genetics
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology
  • Tumor Suppressor Proteins / genetics
  • X-linked Nuclear Protein / genetics

Substances

  • Tumor Suppressor Proteins
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • DNA Modification Methylases
  • MGMT protein, human
  • BCAT1 protein, human
  • Transaminases
  • ATRX protein, human
  • X-linked Nuclear Protein
  • DNA Repair Enzymes