Molecular features of glioblastomas in long-term survivors compared to short-term survivors-a matched-pair analysis

Radiat Oncol. 2022 Jan 24;17(1):15. doi: 10.1186/s13014-022-01984-w.

Abstract

Background: Although glioblastoma (GB) is associated with a devastating prognosis, a small proportion of patients achieve long-term survival rates. We herein present a matched-pair analysis of molecular factors found in long- and short-term survivors (LTS, STS).

Methods: We performed a cross-institutional analysis of 262 patient records and matched a group of 91 LTS (≥ 3 years) with two groups of STS (STS-1, n = 91; STS-2, n = 80). Matching was performed according to age, Karnofsky Performance Status, initial therapy and adjuvant therapy. Molecular factors were compared between LTS (total of 91 patients) v. STS-1, and LTS (subgroup of 80 patients) v. STS-2. We included glial fibrillary acidic protein (GFAP), O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, isocitrate dehydrogenase 1 (IDH-1); furthermore, the proliferation index was analyzed (Ki-67/MIB-1).

Results: IDH-1 and decreased Ki-67 were numerically associated with LTS but the difference was only significant compared to STS-1 (n.s. v. STS-2). LTS was associated with MGMT promoter hypermethylation (p = 0.013 and p = 0.022) and GFAP expression (p < 0.001 and p = 0.001). Positivity for both factors combined compared to negativity for one factor occurred more often in the LTS group (p = 0.002 and p = 0.006); negativity for both factors combined did not occur in the LTS group.

Conclusion: In this retrospective analysis, GFAP expression and MGMT promoter methylation were associated with LTS. Given the hypothesis-generating nature of our study, these observations should be confirmed in prospective clinical trials.

Keywords: GBM; GFAP; Glioblastoma; MGMT; Prognostic factors.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cancer Survivors
  • Child
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glial Fibrillary Acidic Protein / genetics
  • Glioblastoma / genetics*
  • Humans
  • Male
  • Matched-Pair Analysis
  • Middle Aged
  • Retrospective Studies
  • Time Factors
  • Tumor Suppressor Proteins / genetics
  • Young Adult

Substances

  • GFAP protein, human
  • Glial Fibrillary Acidic Protein
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes