Expression Profile of Genes Related to Drug Metabolism in Human Brain Tumors

Pantelis Stavrinou1, Maria-Christina Mavrogiorgou2, Konstantinos Polyzoidis3

  • 1Department of Neurosurgery, University of Cologne, Cologne, Germany.

Plos One
|November 19, 2015
PubMed
Abstract

Insights

Brain tumor subtypes show distinct patterns of drug-metabolizing enzyme expression, with histological type being the primary driver, not malignancy grade. This impacts carcinogen detoxification and susceptibility.

Area of Science:

  • Neuro-oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Phase I and II enzymes metabolize and detoxify compounds, including carcinogens.
  • Enzyme activity is crucial for inactivating carcinogens and determining susceptibility.
  • Expression of these enzymes in human brain tumors is understudied.

Purpose of the Study:

  • To investigate the association between tumor pathology and the expression of seven phase I and II drug-metabolizing genes and their proteins.
  • To analyze the expression profiles of CYP1A1, CYP1B1, ALDH3A1, AOX1, GSTP1, GSTT1, and GSTM3 in human brain tumors.

Main Methods:

  • Gene and protein expression analyzed using qRT-PCR and western blotting.
  • Study cohort included 77 tumors: meningioma, astrocytoma, and brain metastases (lung adenocarcinoma).

Main Results:

  • Meningeal tumors exhibited higher expression of AOX1, CYP1B1, GSTM3, and GSTP1 (gene and protein levels for AOX1, GSTM3, GSTP1).
  • A negative correlation was found between WHO malignancy grade and expression levels of AOX1, GSTM3, and GSTP1.
  • Gene and protein expression correlation observed for AOX1, GSTP1, and GSTM3 in astrocytomas.

Conclusions:

  • Central nervous system (CNS) tumors display varied drug-metabolizing gene expression patterns.
  • Histological subtype is the predominant factor influencing enzyme expression, more so than malignancy grade.
  • Findings suggest subtype-specific roles in detoxification and carcinogen susceptibility within CNS tumors.

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