Prognostic impact of the expression/phosphorylation of the BH3-only proteins of the BCL-2 family in glioblastoma multiforme

Cell Death Dis. 2012 Nov 15;3(11):e421. doi: 10.1038/cddis.2012.150.

Abstract

Apoptosis has a crucial role in anti-cancer treatment. The proteins of the BCL-2 family are core members of the apoptotic program. Thus, we postulated that alterations in the expression of BCL-2 protein family, and in particular in that of the Bcl-2 homology domain 3 (BH3)-only proteins (which can neutralized anti-apoptotic proteins or activate pro-apoptotic proteins) could account for differences in the overall survival (OS) of patients. To test this hypothesis, we analyzed the expression of 15 members of the BCL-2 protein family (Bax, Bak, Bok, Bcl-2, Bcl-xl, Bcl-w, Mcl-1, Bad, Bid, Bim, Bik, Bmf, Hrk, Noxa and Puma) in glioblastoma multiforme (GBM) tumors, the most frequent brain tumor in adults. We found that none of the individual expression of these proteins is associated with a significant variation in OS of the patients. However, when all BH3 proteins were pooled to determine a BH3(score), this score was significantly correlated with OS of GBM patients. We also noted that patients with a have high level of phospho-Bad and phospho-Bim displayed a lower OS. Thus, BH3 scoring/profiling could be used as an independent prognostic factor in GBM when globally analyzed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • BH3 Interacting Domain Death Agonist Protein / genetics*
  • BH3 Interacting Domain Death Agonist Protein / metabolism*
  • Female
  • Glioblastoma / diagnosis
  • Glioblastoma / genetics
  • Glioblastoma / metabolism*
  • Glioblastoma / mortality
  • Humans
  • Male
  • Middle Aged
  • Multigene Family
  • Phosphorylation
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Survival Analysis

Substances

  • BH3 Interacting Domain Death Agonist Protein
  • Proto-Oncogene Proteins c-bcl-2