Immunohistochemical Analysis of DNA Repair- and Drug-Efflux-Associated Molecules in Tumor and Peritumor Areas of Glioblastoma

Int J Mol Sci. 2021 Feb 5;22(4):1620. doi: 10.3390/ijms22041620.

Abstract

Glioblastoma (GBM), the most commonly occurring primary tumor arising within the central nervous system, is characterized by high invasiveness and poor prognosis. In spite of the improvement in surgical techniques, along with the administration of chemo- and radiation therapy and the incessant investigation in search of prospective therapeutic targets, the local recurrence that frequently occurs within the peritumoral brain tissue makes GBM the most malignant and terminal type of astrocytoma. In the current study, we investigated both GBM and peritumoral tissues obtained from 55 hospitalized patients and the expression of three molecules involved in the onset of resistance/unresponsiveness to chemotherapy: O6-methylguanine methyltransferase (MGMT), breast cancer resistance protein (BCRP1), and A2B5. We propose that the expression of these molecules in the peritumoral tissue might be crucial to promoting the development of early tumorigenic events in the tissue surrounding GBM as well as responsible for the recurrence originating in this apparently normal area and, accordingly, for the resistance to treatment with the standard chemotherapeutic regimen. Notably, the inverse correlation found between MGMT expression in peritumoral tissue and patients' survival suggests a prognostic role for this protein.

Keywords: A2B5; BCRP1; MGMT; cancer stem cells; chemotherapy; glioblastoma; peritumoral area.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism*
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / metabolism*
  • DNA Modification Methylases / metabolism*
  • DNA Repair Enzymes / metabolism*
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / metabolism*
  • Hospitalization
  • Humans
  • Male
  • Neoplasm Proteins / metabolism*
  • Prospective Studies
  • Tumor Microenvironment
  • Tumor Suppressor Proteins / metabolism*

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes